rs2856728

Variant names:

• chr7-74056452-C-T
• rs2856728
• NM_000501.4:c.1315+17C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000501.4(ELN):​c.1315+17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.8 in 1,613,490 control chromosomes in the GnomAD database, including 517,464 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.79 (48053 hom., cov: 29)
  • Exomes 𝑓: 0.80 (469411 hom.)
• Consequence: ELN NM_000501.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -3.43
• Publications: 26 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 (BayesDel_noAF=-0.88).
• BP6: Variant 7-74056452-C-T is Benign according to our data. Variant chr7-74056452-C-T is described in ClinVar as Benign. ClinVar VariationId is 213163.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELN	NM_000501.4	c.1315+17C>T		intron_variant	Intron 20 of 32	ENST00000252034.12	NP_000492.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELN	ENST00000252034.12	c.1315+17C>T		intron_variant	Intron 20 of 32	1	NM_000501.4	ENSP00000252034.7

Frequencies

GnomAD3 genomes AF: 0.795 AC: 120563 AN: 151666 Hom.: 48007 Cov.: 29

Gnomad AFR AF: 0.768

Gnomad AMI AF: 0.831

Gnomad AMR AF: 0.801

Gnomad ASJ AF: 0.833

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.712

Gnomad FIN AF: 0.831

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.815

Gnomad OTH AF: 0.808

GnomAD2 exomes AF: 0.789 AC: 198194 AN: 251290 AF XY: 0.785

Gnomad AFR exome AF: 0.763

Gnomad AMR exome AF: 0.777

Gnomad ASJ exome AF: 0.826

Gnomad EAS exome AF: 0.704

Gnomad FIN exome AF: 0.833

Gnomad NFE exome AF: 0.815

Gnomad OTH exome AF: 0.794

GnomAD4 exome AF: 0.801 AC: 1170485 AN: 1461706 Hom.: 469411 Cov.: 61 AF XY: 0.799 AC XY: 580670 AN XY: 727144

African (AFR) AF: 0.761 AC: 25483 AN: 33480

American (AMR) AF: 0.780 AC: 34869 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.832 AC: 21737 AN: 26136

East Asian (EAS) AF: 0.715 AC: 28392 AN: 39700

South Asian (SAS) AF: 0.721 AC: 62187 AN: 86254

European-Finnish (FIN) AF: 0.834 AC: 44562 AN: 53416

Middle Eastern (MID) AF: 0.793 AC: 4536 AN: 5722

European-Non Finnish (NFE) AF: 0.810 AC: 900672 AN: 1111900

Other (OTH) AF: 0.796 AC: 48047 AN: 60382

GnomAD4 genome AF: 0.795 AC: 120659 AN: 151784 Hom.: 48053 Cov.: 29 AF XY: 0.794 AC XY: 58909 AN XY: 74152

African (AFR) AF: 0.768 AC: 31773 AN: 41386

American (AMR) AF: 0.801 AC: 12227 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.833 AC: 2889 AN: 3470

East Asian (EAS) AF: 0.694 AC: 3555 AN: 5126

South Asian (SAS) AF: 0.711 AC: 3414 AN: 4804

European-Finnish (FIN) AF: 0.831 AC: 8756 AN: 10532

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.815 AC: 55352 AN: 67902

Other (OTH) AF: 0.810 AC: 1705 AN: 2104

Alfa AF: 0.806 Hom.: 69489

Bravo AF: 0.791

Asia WGS AF: 0.714 AC: 2488 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:5

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Jun 06, 2017

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Apr 04, 2023

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Cutis laxa, autosomal dominant 1 Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Supravalvar aortic stenosis Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.12
DANN	Benign	0.91
PhyloP100		-3.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2856728; hg19: chr7-73470782;