rs537844185

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000501.4(ELN):c.1264G>A(p.Gly422Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 1,613,756 control chromosomes in the GnomAD database, including 114,461 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 8115 hom., cov: 31)

Exomes 𝑓: 0.37 ( 106346 hom. )

Consequence

ELN
NM_000501.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.709

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=5.096197E-4).

BP6

Variant 7-74056384-G-A is Benign according to our data. Variant chr7-74056384-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 43582.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74056384-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELN	NM_000501.4 link	c.1264G>A	p.Gly422Ser	missense_variant	Exon 20 of 33	ENST00000252034.12	NP_000492.2	P15502-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELN	ENST00000252034.12 link	c.1264G>A	p.Gly422Ser	missense_variant	Exon 20 of 33	1	NM_000501.4	ENSP00000252034.7		P15502-2

Frequencies

GnomAD3 genomes

AF:

0.306

AC:

46496

AN:

151764

Hom.:

8099

Cov.:

show subpopulations

Gnomad AFR

AF:

0.165

Gnomad AMI

AF:

0.445

Gnomad AMR

AF:

0.276

Gnomad ASJ

AF:

0.463

Gnomad EAS

AF:

0.124

Gnomad SAS

AF:

0.225

Gnomad FIN

AF:

0.345

Gnomad MID

AF:

0.411

Gnomad NFE

AF:

0.401

Gnomad OTH

AF:

0.349

GnomAD3 exomes

AF:

0.321

AC:

80822

AN:

251470

Hom.:

14620

AF XY:

0.324

AC XY:

44035

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.164

Gnomad AMR exome

AF:

0.218

Gnomad ASJ exome

AF:

0.459

Gnomad EAS exome

AF:

0.111

Gnomad SAS exome

AF:

0.241

Gnomad FIN exome

AF:

0.354

Gnomad NFE exome

AF:

0.410

Gnomad OTH exome

AF:

0.372

GnomAD4 exome

AF:

0.374

AC:

547143

AN:

1461870

Hom.:

106346

Cov.:

AF XY:

0.371

AC XY:

269755

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.156

Gnomad4 AMR exome

AF:

0.227

Gnomad4 ASJ exome

AF:

0.461

Gnomad4 EAS exome

AF:

0.155

Gnomad4 SAS exome

AF:

0.237

Gnomad4 FIN exome

AF:

0.357

Gnomad4 NFE exome

AF:

0.405

Gnomad4 OTH exome

AF:

0.357

GnomAD4 genome

AF:

0.306

AC:

46541

AN:

151886

Hom.:

8115

Cov.:

AF XY:

0.301

AC XY:

22341

AN XY:

74206

show subpopulations

Gnomad4 AFR

AF:

0.165

Gnomad4 AMR

AF:

0.276

Gnomad4 ASJ

AF:

0.463

Gnomad4 EAS

AF:

0.124

Gnomad4 SAS

AF:

0.226

Gnomad4 FIN

AF:

0.345

Gnomad4 NFE

AF:

0.401

Gnomad4 OTH

AF:

0.356

Alfa

AF:

0.384

Hom.:

24904

Bravo

AF:

0.297

TwinsUK

AF:

0.408

AC:

1513

ALSPAC

AF:

0.406

AC:

1564

ESP6500AA

AF:

0.177

AC:

779

ESP6500EA

AF:

0.413

AC:

3551

ExAC

AF:

0.326

AC:

39602

Asia WGS

AF:

0.244

AC:

847

AN:

3478

EpiCase

AF:

0.406

EpiControl

AF:

0.409

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Jun 06, 2017

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Aug 06, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

p.Gly422Ser in exon 20 of ELN: This variant is not expected to have clinical sig nificance because it has been identified in 42% (27817/66734) of European chromo somes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs2071307). -

Apr 04, 2023

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

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

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

- -

Supravalvar aortic stenosis

Benign:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), 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

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.18

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

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.38

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

MetaRNN

Benign

0.00051

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

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

.;N;N;.;N;.;.;.;.;.;.;N;N

PrimateAI

Benign

0.47

PROVEAN

Benign

-2.0

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

REVEL

Benign

0.038

Sift

Benign

0.13

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

Sift4G

Uncertain

0.042

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

Polyphen

0.012

B;B;.;B;B;B;B;B;B;B;B;B;.

Vest4

0.13

MPC

0.18

ClinPred

0.0019

GERP RS

1.2

Varity_R

0.021

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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