rs140425210

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000501.4(ELN):c.1828G>A(p.Gly610Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000521 in 1,609,756 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0026 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00030 ( 0 hom. )

Consequence

ELN
NM_000501.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 4.92

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009562254).

BP6

Variant 7-74063194-G-A is Benign according to our data. Variant chr7-74063194-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 226631.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00262 (399/152018) while in subpopulation AFR AF= 0.00914 (379/41466). AF 95% confidence interval is 0.00838. There are 3 homozygotes in gnomad4. There are 196 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 399 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELN	NM_000501.4 linkuse as main transcript	c.1828G>A	p.Gly610Ser	missense_variant	27/33	ENST00000252034.12	NP_000492.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELN	ENST00000252034.12 linkuse as main transcript	c.1828G>A	p.Gly610Ser	missense_variant	27/33	1	NM_000501.4	ENSP00000252034	P4	P15502-2

Frequencies

GnomAD3 genomes

AF:

0.00263

AC:

399

AN:

151898

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00917

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000721

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.000697

AC:

168

AN:

240874

Hom.:

AF XY:

0.000493

AC XY:

AN XY:

129872

show subpopulations

Gnomad AFR exome

AF:

0.00926

Gnomad AMR exome

AF:

0.000446

Gnomad ASJ exome

AF:

0.000207

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000348

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000549

Gnomad OTH exome

AF:

0.000343

GnomAD4 exome

AF:

0.000302

AC:

440

AN:

1457738

Hom.:

Cov.:

AF XY:

0.000262

AC XY:

190

AN XY:

724480

show subpopulations

Gnomad4 AFR exome

AF:

0.00884

Gnomad4 AMR exome

AF:

0.000680

Gnomad4 ASJ exome

AF:

0.000348

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0000355

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000333

Gnomad4 OTH exome

AF:

0.000930

GnomAD4 genome

AF:

0.00262

AC:

399

AN:

152018

Hom.:

Cov.:

AF XY:

0.00264

AC XY:

196

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.00914

Gnomad4 AMR

AF:

0.000720

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000589

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.000500

Hom.:

Bravo

AF:

0.00300

ESP6500AA

AF:

0.00908

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000816

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jan 02, 2017	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 19, 2021	This variant is associated with the following publications: (PMID: 23401415) -

Supravalvar aortic stenosis

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 28, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 28, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Feb 15, 2016

p.Gly610Ser in exon 27 of ELN: This variant is not expected to have clinical sig nificance because it has been identified in 1.1% (90/7766) of African chromosome s from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.w ashington.edu/EVS; dbSNP rs140425210). -

Cutis laxa, autosomal dominant 1

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 28, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.16

T;T;.;T;T;.;.;.;.;T;.;.;.;.;.

Eigen

Benign

-0.0078

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.43

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaRNN

Benign

0.0096

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.7

.;.;.;L;.;.;.;.;.;.;.;.;.;.;.

MutationTaster

Benign

0.97

N;N;N;N;N;N;N;N;N;N;N;N;N;N;N

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.8

N;.;N;D;N;N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.10

Sift

Benign

0.34

T;.;T;D;D;T;.;T;T;D;D;T;.;D;D

Sift4G

Uncertain

0.047

D;D;T;D;D;T;T;T;D;T;T;T;T;D;T

Polyphen

0.97

D;D;D;.;D;D;D;D;D;D;D;D;D;D;.

Vest4

0.40

MVP

0.75

MPC

0.18

ClinPred

0.032

GERP RS

3.8

Varity_R

0.067

gMVP

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over