7-74053320-CTGTGTGTGTGTGTGTGTGTGTG-CTGTGTGTGTGTGTGTGTG

Position:

• chr7-74053320-CTGTGTGTGTGTGTGTGTGTGTG-CTGTGTGTGTGTGTGTGTG

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000501.4(ELN):​c.1096+47_1096+50del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (21045 hom., cov: 0)
  • Exomes 𝑓: 0.40 (1367 hom.)
  • Failed GnomAD Quality Control
• Consequence: ELN NM_000501.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• 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 -16 ACMG points.

• BP6: Variant 7-74053320-CTGTG-C is Benign according to our data. Variant chr7-74053320-CTGTG-C is described in ClinVar as [Benign]. Clinvar id is 402825.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74053320-CTGTG-C is described in Lovd as [Benign]. Variant chr7-74053320-CTGTG-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELN	NM_000501.4	c.1096+47_1096+50del		intron_variant		ENST00000252034.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELN	ENST00000252034.12	c.1096+47_1096+50del		intron_variant		1	NM_000501.4	P4

Frequencies

GnomAD3 genomes AF: 0.546 AC: 78542 AN: 143916 Hom.: 21037 Cov.: 0

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.506

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.572

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.561

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.398 AC: 563021 AN: 1414038 Hom.: 1367 AF XY: 0.397 AC XY: 278243 AN XY: 700706

Gnomad4 AFR exome AF: 0.364

Gnomad4 AMR exome AF: 0.395

Gnomad4 ASJ exome AF: 0.415

Gnomad4 EAS exome AF: 0.403

Gnomad4 SAS exome AF: 0.387

Gnomad4 FIN exome AF: 0.410

Gnomad4 NFE exome AF: 0.399

Gnomad4 OTH exome AF: 0.399

GnomAD4 genome AF: 0.546 AC: 78583 AN: 144018 Hom.: 21045 Cov.: 0 AF XY: 0.547 AC XY: 38210 AN XY: 69822

Gnomad4 AFR AF: 0.486

Gnomad4 AMR AF: 0.601

Gnomad4 ASJ AF: 0.607

Gnomad4 EAS AF: 0.572

Gnomad4 SAS AF: 0.541

Gnomad4 FIN AF: 0.576

Gnomad4 NFE AF: 0.559

Gnomad4 OTH AF: 0.563

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 18, 2019

- -

Supravalvar aortic stenosis Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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;