NM_000501.4:c.2132G>A

Variant names:

Variant summary

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

The NM_000501.4(ELN):c.2132G>A(p.Gly711Asp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00425 in 1,614,152 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0044 ( 17 hom. )

Consequence

ELN
NM_000501.4 missense, splice_region

Scores

Splicing: ADA: 0.006857

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 1.05

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=0.011181653).

BP6

Variant 7-74068657-G-A is Benign according to our data. Variant chr7-74068657-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 43585.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-74068657-G-A is described in Lovd as [Likely_benign]. Variant chr7-74068657-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00316 (481/152288) while in subpopulation AMR AF= 0.00562 (86/15290). AF 95% confidence interval is 0.00466. There are 0 homozygotes in gnomad4. There are 225 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 481 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELN	NM_000501.4 link	c.2132G>A	p.Gly711Asp	missense_variant, splice_region_variant	Exon 33 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.2132G>A	p.Gly711Asp	missense_variant, splice_region_variant	Exon 33 of 33	1	NM_000501.4	ENSP00000252034.7		P15502-2

Frequencies

GnomAD3 genomes

AF:

0.00316

AC:

481

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000941

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00563

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00497

Gnomad OTH

AF:

0.00670

GnomAD3 exomes

AF:

0.00305

AC:

765

AN:

251040

Hom.:

AF XY:

0.00287

AC XY:

389

AN XY:

135718

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.00480

Gnomad ASJ exome

AF:

0.000397

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.00498

Gnomad OTH exome

AF:

0.00326

GnomAD4 exome

AF:

0.00436

AC:

6380

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00417

AC XY:

3032

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.000836

Gnomad4 AMR exome

AF:

0.00519

Gnomad4 ASJ exome

AF:

0.000497

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.00527

Gnomad4 OTH exome

AF:

0.00376

GnomAD4 genome

AF:

0.00316

AC:

481

AN:

152288

Hom.:

Cov.:

AF XY:

0.00302

AC XY:

225

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.000938

Gnomad4 AMR

AF:

0.00562

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00497

Gnomad4 OTH

AF:

0.00663

Alfa

AF:

0.00408

Hom.:

Bravo

AF:

0.00352

TwinsUK

AF:

0.00512

AC:

ALSPAC

AF:

0.00571

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00395

AC:

ExAC

AF:

0.00287

AC:

349

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00485

EpiControl

AF:

0.00516

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Mar 09, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 16374472, 16081882, 19029017, 28146470) -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ELN: BS1, BS2 -

not specified

Benign:3

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jul 19, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Gly711Asp in exon 33 of ELN: This variant is not expected to have clinical signi ficance because it has been identified in 0.4% (34/8600) of European American ch romosomes from a broad population by the NHLBI Exome Sequencing Project (http:// evs.gs.washington.edu/EVS) and in 2.5% (5/196) of Tuscan (Italian) chromosomes f rom a broad population by the 1000 Genomes project (dbSNP rs41511151). Gly711A sp in exon 33 of ELN (rs41511151; allele frequency = 0.4%, 34/8600) ** -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Supravalvar aortic stenosis

Benign:3

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 28, 2019

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cutis laxa, autosomal dominant

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.64

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.10

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.13

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

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.69

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

MetaRNN

Benign

0.011

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

MetaSVM

Benign

-0.67

MutationAssessor

Benign

1.6

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

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-2.0

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

REVEL

Uncertain

0.34

Sift

Pathogenic

0.0

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

Sift4G

Uncertain

0.0030

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

Polyphen

0.99

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

Vest4

0.51

MVP

0.82

MPC

0.24

ClinPred

0.045

GERP RS

2.6

Varity_R

0.069

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0069

dbscSNV1_RF

Benign

0.17

SpliceAI score (max)

0.090

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