rs5351

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001122659.3(EDNRB):c.831A>G(p.Leu277Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 1,610,368 control chromosomes in the GnomAD database, including 293,077 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.58 ( 25616 hom., cov: 32)

Exomes 𝑓: 0.60 ( 267461 hom. )

Consequence

EDNRB
NM_001122659.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.124

Variant links:

Genes affected

EDNRB (HGNC:3180): (endothelin receptor type B) The protein encoded by this gene is a G protein-coupled receptor which activates a phosphatidylinositol-calcium second messenger system. Its ligand, endothelin, consists of a family of three potent vasoactive peptides: ET1, ET2, and ET3. Studies suggest that the multigenic disorder, Hirschsprung disease type 2, is due to mutations in the endothelin receptor type B gene. Alternative splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Oct 2016]

EDNRB links:

EDNRB-AS1 (HGNC:49045): (EDNRB antisense RNA 1)

EDNRB-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 13-77901178-T-C is Benign according to our data. Variant chr13-77901178-T-C is described in ClinVar as [Benign]. Clinvar id is 226622.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-77901178-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.124 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDNRB	NM_001122659.3 link	c.831A>G	p.Leu277Leu	synonymous_variant	Exon 4 of 7	ENST00000646607.2	NP_001116131.1	P24530-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EDNRB	ENST00000646607.2 link	c.831A>G	p.Leu277Leu	synonymous_variant	Exon 4 of 7		NM_001122659.3	ENSP00000493527.1		P24530-1

Frequencies

GnomAD3 genomes

AF:

0.578

AC:

87644

AN:

151594

Hom.:

25610

Cov.:

show subpopulations

Gnomad AFR

AF:

0.540

Gnomad AMI

AF:

0.635

Gnomad AMR

AF:

0.566

Gnomad ASJ

AF:

0.508

Gnomad EAS

AF:

0.348

Gnomad SAS

AF:

0.544

Gnomad FIN

AF:

0.598

Gnomad MID

AF:

0.615

Gnomad NFE

AF:

0.623

Gnomad OTH

AF:

0.572

GnomAD3 exomes

AF:

0.574

AC:

143733

AN:

250254

Hom.:

42171

AF XY:

0.574

AC XY:

77686

AN XY:

135338

show subpopulations

Gnomad AFR exome

AF:

0.546

Gnomad AMR exome

AF:

0.583

Gnomad ASJ exome

AF:

0.511

Gnomad EAS exome

AF:

0.330

Gnomad SAS exome

AF:

0.555

Gnomad FIN exome

AF:

0.599

Gnomad NFE exome

AF:

0.621

Gnomad OTH exome

AF:

0.583

GnomAD4 exome

AF:

0.603

AC:

879869

AN:

1458656

Hom.:

267461

Cov.:

AF XY:

0.601

AC XY:

436238

AN XY:

725736

show subpopulations

Gnomad4 AFR exome

AF:

0.547

Gnomad4 AMR exome

AF:

0.579

Gnomad4 ASJ exome

AF:

0.509

Gnomad4 EAS exome

AF:

0.397

Gnomad4 SAS exome

AF:

0.552

Gnomad4 FIN exome

AF:

0.606

Gnomad4 NFE exome

AF:

0.621

Gnomad4 OTH exome

AF:

0.579

GnomAD4 genome

AF:

0.578

AC:

87681

AN:

151712

Hom.:

25616

Cov.:

AF XY:

0.574

AC XY:

42509

AN XY:

74120

show subpopulations

Gnomad4 AFR

AF:

0.540

Gnomad4 AMR

AF:

0.567

Gnomad4 ASJ

AF:

0.508

Gnomad4 EAS

AF:

0.347

Gnomad4 SAS

AF:

0.544

Gnomad4 FIN

AF:

0.598

Gnomad4 NFE

AF:

0.623

Gnomad4 OTH

AF:

0.569

Alfa

AF:

0.589

Hom.:

13821

Bravo

AF:

0.574

Asia WGS

AF:

0.490

AC:

1702

AN:

3470

EpiCase

AF:

0.612

EpiControl

AF:

0.610

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Leu367Leu in exon 5 of EDNRB: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 43.5% (1916/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs5351). -

May 09, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Hirschsprung disease, susceptibility to, 2

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

5.2

DANN

Benign

0.78

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

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