rs2856728

Positions:

• chr7-74056452-C-T

Variant summary

Our verdict is Benign. Variant got -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:7
• Conservation: PhyloP100: -3.43

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 -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 id is 213163.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74056452-C-T is described in Lovd as [Benign].
• 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/exons	MANE	UniProt
ELN	NM_000501.4	c.1315+17C>T		intron_variant		ENST00000252034.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELN	ENST00000252034.12	c.1315+17C>T		intron_variant		1	NM_000501.4	P4

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

GnomAD3 exomes AF: 0.789 AC: 198194 AN: 251290 Hom.: 78421 AF XY: 0.785 AC XY: 106626 AN XY: 135826

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 SAS exome AF: 0.724

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

Gnomad4 AFR exome AF: 0.761

Gnomad4 AMR exome AF: 0.780

Gnomad4 ASJ exome AF: 0.832

Gnomad4 EAS exome AF: 0.715

Gnomad4 SAS exome AF: 0.721

Gnomad4 FIN exome AF: 0.834

Gnomad4 NFE exome AF: 0.810

Gnomad4 OTH exome AF: 0.796

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

Gnomad4 AFR AF: 0.768

Gnomad4 AMR AF: 0.801

Gnomad4 ASJ AF: 0.833

Gnomad4 EAS AF: 0.694

Gnomad4 SAS AF: 0.711

Gnomad4 FIN AF: 0.831

Gnomad4 NFE AF: 0.815

Gnomad4 OTH AF: 0.810

Alfa AF: 0.805 Hom.: 57816

Bravo AF: 0.791

Asia WGS AF: 0.714 AC: 2488 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:5

Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Apr 04, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 06, 2017	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Cutis laxa, autosomal dominant 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Supravalvar aortic stenosis Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.12
DANN	Benign	0.91

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

Publications

LitVar

Other links and lift over

dbSNP: rs2856728; hg19: chr7-73470782;