7-74053320-CTGTGTGTGTGTGTGTGTGTGTG-CTGTGTGTGTGTG

Position:

• chr7-74053320-CTGTGTGTGTGTGTGTGTGTGTG-CTGTGTGTGTGTG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_000501.4(ELN):​c.1096+41_1096+50del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00014 in 1,562,560 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00030 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: ELN NM_000501.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000298 (43/144250) while in subpopulation AFR AF= 0.000774 (30/38764). AF 95% confidence interval is 0.000556. There are 0 homozygotes in gnomad4. There are 21 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 43 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELN	NM_000501.4	c.1096+41_1096+50del		intron_variant		ENST00000252034.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELN	ENST00000252034.12	c.1096+41_1096+50del		intron_variant		1	NM_000501.4	P4

Frequencies

GnomAD3 genomes AF: 0.000298 AC: 43 AN: 144146 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000776

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000278

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000408

Gnomad SAS AF: 0.000228

Gnomad FIN AF: 0.000212

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000456

Gnomad OTH AF: 0.000507

GnomAD4 exome AF: 0.000124 AC: 176 AN: 1418310 Hom.: 0 AF XY: 0.000124 AC XY: 87 AN XY: 702902

Gnomad4 AFR exome AF: 0.000989

Gnomad4 AMR exome AF: 0.000177

Gnomad4 ASJ exome AF: 0.0000395

Gnomad4 EAS exome AF: 0.0000796

Gnomad4 SAS exome AF: 0.000121

Gnomad4 FIN exome AF: 0.000550

Gnomad4 NFE exome AF: 0.0000771

Gnomad4 OTH exome AF: 0.000188

GnomAD4 genome AF: 0.000298 AC: 43 AN: 144250 Hom.: 0 Cov.: 0 AF XY: 0.000300 AC XY: 21 AN XY: 69950

Gnomad4 AFR AF: 0.000774

Gnomad4 AMR AF: 0.000277

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000409

Gnomad4 SAS AF: 0.000229

Gnomad4 FIN AF: 0.000212

Gnomad4 NFE AF: 0.0000456

Gnomad4 OTH AF: 0.000501

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10579871; hg19: chr7-73467650;