Variant 4-147542593-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BP4_ModerateBP6_Moderate

The NM_001957.4(EDNRA):c.1259G>C(p.Ser420Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000078 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

EDNRA
NM_001957.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.37

Variant links:

Genes affected

EDNRA (HGNC:3179): (endothelin receptor type A) This gene encodes the receptor for endothelin-1, a peptide that plays a role in potent and long-lasting vasoconstriction. This receptor associates with guanine-nucleotide-binding (G) proteins, and this coupling activates a phosphatidylinositol-calcium second messenger system. Polymorphisms in this gene have been linked to migraine headache resistance. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

EDNRA links:

EDNRA (HGNC:):

EDNRA links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), EDNRA. . Gene score misZ 2.8025 (greater than the threshold 3.09). Trascript score misZ 3.9779 (greater than threshold 3.09). GenCC has associacion of gene with mandibulofacial dysostosis with alopecia.

BP4

Computational evidence support a benign effect (MetaRNN=0.22435942).

BP6

Variant 4-147542593-G-C is Benign according to our data. Variant chr4-147542593-G-C is described in ClinVar as [Benign]. Clinvar id is 1685008.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EDNRA	NM_001957.4 linkuse as main transcript	c.1259G>C	p.Ser420Thr	missense_variant	8/8	ENST00000651419.1	NP_001948.1	P25101-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EDNRA	ENST00000651419.1 linkuse as main transcript	c.1259G>C	p.Ser420Thr	missense_variant	8/8		NM_001957.4	ENSP00000498969.1		P25101-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000781

AC:

114

AN:

1460288

Hom.:

Cov.:

AF XY:

0.0000675

AC XY:

AN XY:

726422

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00151

Gnomad4 NFE exome

AF:

0.0000171

Gnomad4 OTH exome

AF:

0.000266

GnomAD4 genome

Cov.:

ExAC

AF:

0.000297

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Uncertain

0.071

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.41

T;.;.;.;.

Eigen

Uncertain

0.66

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.84

T;T;.;T;.

MetaRNN

Benign

0.22

T;T;T;T;T

MetaSVM

Uncertain

-0.10

MutationAssessor

Uncertain

2.5

M;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.1

N;N;N;.;N

REVEL

Pathogenic

0.69

Sift

Uncertain

0.027

D;T;D;.;T

Sift4G

Benign

0.078

T;T;T;.;T

Polyphen

1.0

D;D;.;.;D

Vest4

0.37

MVP

0.70

MPC

1.6

ClinPred

0.022

GERP RS

5.5

Varity_R

0.34

gMVP

0.61

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