Variant 4-147485739-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001957.4(EDNRA):c.58A>G(p.Ser20Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

EDNRA
NM_001957.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0800

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.060783297).

BS2

High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDNRA	NM_001957.4 link	c.58A>G	p.Ser20Gly	missense_variant	Exon 2 of 8	ENST00000651419.1	NP_001948.1	P25101-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EDNRA	ENST00000651419.1 link	c.58A>G	p.Ser20Gly	missense_variant	Exon 2 of 8		NM_001957.4	ENSP00000498969.1		P25101-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461768

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Aug 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.58A>G (p.S20G) alteration is located in exon 2 (coding exon 1) of the EDNRA gene. This alteration results from a A to G substitution at nucleotide position 58, causing the serine (S) at amino acid position 20 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

9.3

DANN

Benign

0.97

DEOGEN2

Benign

0.30

T;.;.

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.62

T;T;.

M_CAP

Benign

0.014

MetaRNN

Benign

0.061

T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

0.90

L;L;L

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.37

N;N;N

REVEL

Benign

0.069

Sift

Benign

0.060

T;D;D

Sift4G

Benign

0.40

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.095

MutPred

0.33

Loss of relative solvent accessibility (P = 0.0306);Loss of relative solvent accessibility (P = 0.0306);Loss of relative solvent accessibility (P = 0.0306);

MVP

0.58

MPC

0.84

ClinPred

0.087

GERP RS

-2.6

Varity_R

0.053

gMVP

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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