NM_000501.4:c.1096+35_1096+50delGTGTGTGTGTGTGTGT

Variant names:

• chr7-74053320-CTGTGTGTGTGTGTGTG-C
• rs10579871
• NM_000501.4:c.1096+35_1096+50delGTGTGTGTGTGTGTGT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_000501.4(ELN):​c.1096+35_1096+50delGTGTGTGTGTGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000154 in 1,562,760 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000035 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: ELN NM_000501.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33
• Publications: 3 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELN	NM_000501.4	c.1096+35_1096+50delGTGTGTGTGTGTGTGT		intron_variant	Intron 18 of 32	ENST00000252034.12	NP_000492.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELN	ENST00000252034.12	c.1096+12_1096+27delTGTGTGTGTGTGTGTG		intron_variant	Intron 18 of 32	1	NM_000501.4	ENSP00000252034.7

Frequencies

GnomAD3 genomes AF: 0.0000347 AC: 5 AN: 144146 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000517

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000204

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000304

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000134 AC: 19 AN: 1418614 Hom.: 0 AF XY: 0.0000142 AC XY: 10 AN XY: 703072

African (AFR) AF: 0.0000618 AC: 2 AN: 32370

American (AMR) AF: 0.0000253 AC: 1 AN: 39504

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25306

East Asian (EAS) AF: 0.000133 AC: 5 AN: 37718

South Asian (SAS) AF: 0.0000485 AC: 4 AN: 82512

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49148

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4234

European-Non Finnish (NFE) AF: 0.00000551 AC: 6 AN: 1089286

Other (OTH) AF: 0.0000171 AC: 1 AN: 58536

GnomAD4 genome AF: 0.0000347 AC: 5 AN: 144146 Hom.: 0 Cov.: 0 AF XY: 0.0000143 AC XY: 1 AN XY: 69834

African (AFR) AF: 0.0000517 AC: 2 AN: 38648

American (AMR) AF: 0.00 AC: 0 AN: 14414

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3392

East Asian (EAS) AF: 0.000204 AC: 1 AN: 4900

South Asian (SAS) AF: 0.00 AC: 0 AN: 4382

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9436

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 304

European-Non Finnish (NFE) AF: 0.0000304 AC: 2 AN: 65808

Other (OTH) AF: 0.00 AC: 0 AN: 1974

Alfa AF: 0.00 Hom.: 744

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3

Splicing

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

Other links and lift over

dbSNP: rs10579871; hg19: chr7-73467650;