Variant chr4-147540002-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001957.4(EDNRA):c.1034+52T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00277 in 1,544,072 control chromosomes in the GnomAD database, including 85 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 45 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 40 hom. )

Consequence

EDNRA
NM_001957.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.574

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:

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 (BayesDel_noAF=-0.87).

BP6

Variant 4-147540002-T-C is Benign according to our data. Variant chr4-147540002-T-C is described in ClinVar as [Benign]. Clinvar id is 1235906.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EDNRA	NM_001957.4 linkuse as main transcript	c.1034+52T>C		intron_variant		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.1034+52T>C		intron_variant			NM_001957.4	ENSP00000498969.1		P25101-1

Frequencies

GnomAD3 genomes

AF:

0.0143

AC:

2181

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0494

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00524

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.0167

GnomAD3 exomes

AF:

0.00435

AC:

857

AN:

196822

Hom.:

AF XY:

0.00331

AC XY:

354

AN XY:

106822

show subpopulations

Gnomad AFR exome

AF:

0.0517

Gnomad AMR exome

AF:

0.00274

Gnomad ASJ exome

AF:

0.00103

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000258

Gnomad OTH exome

AF:

0.00199

GnomAD4 exome

AF:

0.00151

AC:

2098

AN:

1391804

Hom.:

Cov.:

AF XY:

0.00135

AC XY:

932

AN XY:

688272

show subpopulations

Gnomad4 AFR exome

AF:

0.0531

Gnomad4 AMR exome

AF:

0.00316

Gnomad4 ASJ exome

AF:

0.00113

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000548

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000134

Gnomad4 OTH exome

AF:

0.00343

GnomAD4 genome

AF:

0.0144

AC:

2186

AN:

152268

Hom.:

Cov.:

AF XY:

0.0137

AC XY:

1023

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0493

Gnomad4 AMR

AF:

0.00523

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.0166

Alfa

AF:

0.00747

Hom.:

Bravo

AF:

0.0164

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

7.7

DANN

Benign

0.38

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