NM_001122659.3:c.552T>C

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001122659.3(EDNRB):c.552T>C(p.Ser184Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.997 in 1,612,874 control chromosomes in the GnomAD database, including 801,580 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.99 ( 73855 hom., cov: 31)

Exomes 𝑓: 1.0 ( 727725 hom. )

Consequence

EDNRB
NM_001122659.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.81

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 13-77903539-A-G is Benign according to our data. Variant chr13-77903539-A-G is described in ClinVar as [Benign]. Clinvar id is 226625.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-77903539-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.81 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDNRB	NM_001122659.3 link	c.552T>C	p.Ser184Ser	synonymous_variant	Exon 2 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.552T>C	p.Ser184Ser	synonymous_variant	Exon 2 of 7		NM_001122659.3	ENSP00000493527.1		P24530-1

Frequencies

GnomAD3 genomes

AF:

0.985

AC:

149684

AN:

151896

Hom.:

73796

Cov.:

show subpopulations

Gnomad AFR

AF:

0.951

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.992

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.994

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.997

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.989

GnomAD3 exomes

AF:

0.996

AC:

249287

AN:

250374

Hom.:

124122

AF XY:

0.996

AC XY:

134828

AN XY:

135308

show subpopulations

Gnomad AFR exome

AF:

0.951

Gnomad AMR exome

AF:

0.997

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.995

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

0.997

GnomAD4 exome

AF:

0.998

AC:

1458106

AN:

1460860

Hom.:

727725

Cov.:

AF XY:

0.998

AC XY:

725418

AN XY:

726756

show subpopulations

Gnomad4 AFR exome

AF:

0.950

Gnomad4 AMR exome

AF:

0.997

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.994

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

0.996

GnomAD4 genome

AF:

0.985

AC:

149802

AN:

152014

Hom.:

73855

Cov.:

AF XY:

0.986

AC XY:

73250

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.951

Gnomad4 AMR

AF:

0.992

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.994

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

1.00

Gnomad4 OTH

AF:

0.990

Alfa

AF:

0.994

Hom.:

37982

Bravo

AF:

0.984

Asia WGS

AF:

0.997

AC:

3468

AN:

3478

EpiCase

AF:

1.00

EpiControl

AF:

1.00

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Ser274Ser in exon 3 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 4.4% (194/4406) of A frican American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs5348). -

ABCD syndrome

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

ABCD syndrome;C1838564:Hirschsprung disease, susceptibility to, 2;C1848519:Waardenburg syndrome type 4A

Benign:1

Oct 25, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Waardenburg syndrome type 4A

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

5.0

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

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