7-74053320-CTGTGTGTGTGTGTGTGTGTGTG-CTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTG

Position:

• chr7-74053320-CTGTGTGTGTGTGTGTGTGTGTG-CTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_000501.4(ELN):​c.1096+41_1096+50dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00064 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00037 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ELN NM_000501.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.780

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 -10 ACMG points.

• BP6: Variant 7-74053320-C-CTGTGTGTGTG is Benign according to our data. Variant chr7-74053320-C-CTGTGTGTGTG is described in ClinVar as [Likely_benign]. Clinvar id is 1631629.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000638 (92/144248) while in subpopulation AFR AF= 0.000955 (37/38762). AF 95% confidence interval is 0.000712. There are 0 homozygotes in gnomad4. There are 40 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 92 AD gene.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.000638 AC: 92 AN: 144144 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000957

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000208

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000228

Gnomad FIN AF: 0.000106

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000760

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000367 AC: 520 AN: 1418058 Hom.: 0 Cov.: 0 AF XY: 0.000353 AC XY: 248 AN XY: 702794

Gnomad4 AFR exome AF: 0.000742

Gnomad4 AMR exome AF: 0.000253

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000436

Gnomad4 FIN exome AF: 0.000142

Gnomad4 NFE exome AF: 0.000388

Gnomad4 OTH exome AF: 0.000359

GnomAD4 genome AF: 0.000638 AC: 92 AN: 144248 Hom.: 0 Cov.: 0 AF XY: 0.000572 AC XY: 40 AN XY: 69948

Gnomad4 AFR AF: 0.000955

Gnomad4 AMR AF: 0.000208

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000229

Gnomad4 FIN AF: 0.000106

Gnomad4 NFE AF: 0.000760

Gnomad4 OTH AF: 0.00

Bravo AF: 0.000646

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Supravalvar aortic stenosis Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Sep 15, 2022

- -

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;