rs28763986

chr7-74057720-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.1414+24C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 1,611,374 control chromosomes in the GnomAD database, including 259,425 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.60 (28146 hom., cov: 31)
  • Exomes 𝑓: 0.56 (231279 hom.)
• Consequence: ELN NM_000501.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.37

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=-0.89).
• BP6: Variant 7-74057720-C-T is Benign according to our data. Variant chr7-74057720-C-T is described in ClinVar as [Benign]. Clinvar id is 1249499.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELN	NM_000501.4	c.1414+24C>T		intron_variant		ENST00000252034.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELN	ENST00000252034.12	c.1414+24C>T		intron_variant		1	NM_000501.4	P4

Frequencies

GnomAD3 genomes AF: 0.604 AC: 91768 AN: 151840 Hom.: 28115 Cov.: 31

Gnomad AFR AF: 0.694

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.701

Gnomad SAS AF: 0.682

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.549

Gnomad OTH AF: 0.576

GnomAD3 exomes AF: 0.590 AC: 147337 AN: 249772 Hom.: 44055 AF XY: 0.592 AC XY: 80147 AN XY: 135280

Gnomad AFR exome AF: 0.699

Gnomad AMR exome AF: 0.573

Gnomad ASJ exome AF: 0.522

Gnomad EAS exome AF: 0.712

Gnomad SAS exome AF: 0.672

Gnomad FIN exome AF: 0.598

Gnomad NFE exome AF: 0.544

Gnomad OTH exome AF: 0.559

GnomAD4 exome AF: 0.560 AC: 817610 AN: 1459414 Hom.: 231279 Cov.: 43 AF XY: 0.564 AC XY: 409615 AN XY: 726036

Gnomad4 AFR exome AF: 0.698

Gnomad4 AMR exome AF: 0.574

Gnomad4 ASJ exome AF: 0.521

Gnomad4 EAS exome AF: 0.704

Gnomad4 SAS exome AF: 0.673

Gnomad4 FIN exome AF: 0.601

Gnomad4 NFE exome AF: 0.540

Gnomad4 OTH exome AF: 0.573

GnomAD4 genome AF: 0.604 AC: 91837 AN: 151960 Hom.: 28146 Cov.: 31 AF XY: 0.609 AC XY: 45210 AN XY: 74268

Gnomad4 AFR AF: 0.694

Gnomad4 AMR AF: 0.577

Gnomad4 ASJ AF: 0.519

Gnomad4 EAS AF: 0.701

Gnomad4 SAS AF: 0.680

Gnomad4 FIN AF: 0.606

Gnomad4 NFE AF: 0.549

Gnomad4 OTH AF: 0.570

Alfa AF: 0.570 Hom.: 6549

Bravo AF: 0.606

Asia WGS AF: 0.599 AC: 2083 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Cutis laxa, autosomal dominant 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.11
Dann	Benign	0.63

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: rs28763986; hg19: chr7-73472050; COSMIC: COSV52709669; COSMIC: COSV52709669;