chr7-74041231-C-T

Variant names:

• chr7-74041231-C-T
• rs41350445
• NM_000501.4:c.212C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000501.4(ELN):​c.212C>T​(p.Ala71Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000827 in 1,613,956 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A71A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0010 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00081 (8 hom.)
• Consequence: ELN NM_000501.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.0390
• Publications: 11 publications found

Genes affected

ELN (HGNC:3327): (elastin) This gene encodes a protein that is one of the two components of elastic fibers. Elastic fibers comprise part of the extracellular matrix and confer elasticity to organs and tissues including the heart, skin, lungs, ligaments, and blood vessels. The encoded protein is rich in hydrophobic amino acids such as glycine and proline, which form mobile hydrophobic regions bounded by crosslinks between lysine residues. Degradation products of the encoded protein, known as elastin-derived peptides or elastokines, bind the elastin receptor complex and other receptors and stimulate migration and proliferation of monocytes and skin fibroblasts. Elastokines can also contribute to cancer progression. Deletions and mutations in this gene are associated with supravalvular aortic stenosis (SVAS) and autosomal dominant cutis laxa. [provided by RefSeq, Aug 2017]

ELN Gene-Disease associations (from GenCC):

• cutis laxa, autosomal dominant 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, Genomics England PanelApp, G2P
• supravalvular aortic stenosis

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• autosomal dominant cutis laxa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• familial thoracic aortic aneurysm and aortic dissection

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003741473).
• BP6: Variant 7-74041231-C-T is Benign according to our data. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74041231-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 43584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000998 (152/152298) while in subpopulation EAS AF = 0.0195 (101/5178). AF 95% confidence interval is 0.0164. There are 0 homozygotes in GnomAd4. There are 83 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 152 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELN	NM_000501.4	c.212C>T	p.Ala71Val	missense_variant	Exon 5 of 33	ENST00000252034.12	NP_000492.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELN	ENST00000252034.12	c.212C>T	p.Ala71Val	missense_variant	Exon 5 of 33	1	NM_000501.4	ENSP00000252034.7

Frequencies

GnomAD3 genomes AF: 0.000999 AC: 152 AN: 152180 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0195

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00141

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00164 AC: 412 AN: 251460 AF XY: 0.00161

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0183

Gnomad FIN exome AF: 0.000831

Gnomad NFE exome AF: 0.000273

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000809 AC: 1182 AN: 1461658 Hom.: 8 Cov.: 31 AF XY: 0.000807 AC XY: 587 AN XY: 727130

African (AFR) AF: 0.0000896 AC: 3 AN: 33468

American (AMR) AF: 0.000313 AC: 14 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.0227 AC: 901 AN: 39694

South Asian (SAS) AF: 0.000464 AC: 40 AN: 86250

European-Finnish (FIN) AF: 0.000562 AC: 30 AN: 53390

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.000135 AC: 150 AN: 1111868

Other (OTH) AF: 0.000662 AC: 40 AN: 60380

GnomAD4 genome AF: 0.000998 AC: 152 AN: 152298 Hom.: 0 Cov.: 32 AF XY: 0.00111 AC XY: 83 AN XY: 74460

African (AFR) AF: 0.0000481 AC: 2 AN: 41566

American (AMR) AF: 0.000131 AC: 2 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.0195 AC: 101 AN: 5178

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4828

European-Finnish (FIN) AF: 0.00141 AC: 15 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000412 AC: 28 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000479 Hom.: 1

Bravo AF: 0.00105

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00164 AC: 199

Asia WGS AF: 0.00577 AC: 20 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Apr 16, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Ala71Val in exon 5 of ELN: This variant has been reported in 2 Asian individual' s with isolated congenital ductus arteriosus aneurysm (Jan 2009). However, it is not expected to have clinical significance because it has been identified in 0. 9% (20/2222) of chromosomes from a broad, unspecified population (dbSNP rs413504 45). -

-

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Supravalvar aortic stenosis Benign:2

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

-

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Cutis laxa, autosomal dominant 1 Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

ELN-related disorder Benign:1

May 15, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	6.9
DANN	Benign	0.73
DEOGEN2	Benign	0.086	T;T;.;T;.;.;.;.;T;.;.;.;.;.;.;T;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.52	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaRNN	Benign	0.0037	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.6	.;.;L;L;.;L;.;L;.;L;.;L;.;L;L;.;L
PhyloP100		-0.039
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.51	N;.;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.19
Sift	Benign	0.43	T;.;T;T;T;.;T;T;T;T;T;T;T;.;T;T;T
Sift4G	Benign	0.096	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.0070	B;B;B;.;B;B;B;B;B;B;.;B;.;B;B;.;.
Vest4		0.20
MVP		0.44
MPC		0.18
ClinPred		0.0078	T
GERP RS		-3.3
Varity_R		0.018
gMVP		0.36
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs41350445; hg19: chr7-73455561; COSMIC: COSV52712556; COSMIC: COSV52712556;