Variant rs5334 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001957.4(EDNRA):c.1005G>A(p.Glu335=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 1,608,528 control chromosomes in the GnomAD database, including 64,432 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 10502 hom., cov: 31)

Exomes 𝑓: 0.26 ( 53930 hom. )

Consequence

EDNRA
NM_001957.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.41

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:

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=-0.41).

BP6

Variant 4-147539921-G-A is Benign according to our data. Variant chr4-147539921-G-A is described in ClinVar as [Benign]. Clinvar id is 1255371.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.41 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.565 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.1005G>A	p.Glu335=	synonymous_variant	6/8	ENST00000651419.1	NP_001948.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EDNRA	ENST00000651419.1 linkuse as main transcript	c.1005G>A	p.Glu335=	synonymous_variant	6/8		NM_001957.4	ENSP00000498969	P1	P25101-1

Frequencies

GnomAD3 genomes

AF:

0.341

AC:

51704

AN:

151758

Hom.:

10492

Cov.:

show subpopulations

Gnomad AFR

AF:

0.572

Gnomad AMI

AF:

0.321

Gnomad AMR

AF:

0.301

Gnomad ASJ

AF:

0.299

Gnomad EAS

AF:

0.217

Gnomad SAS

AF:

0.335

Gnomad FIN

AF:

0.177

Gnomad MID

AF:

0.306

Gnomad NFE

AF:

0.247

Gnomad OTH

AF:

0.334

GnomAD3 exomes

AF:

0.278

AC:

68835

AN:

247346

Hom.:

10837

AF XY:

0.276

AC XY:

36828

AN XY:

133648

show subpopulations

Gnomad AFR exome

AF:

0.576

Gnomad AMR exome

AF:

0.319

Gnomad ASJ exome

AF:

0.298

Gnomad EAS exome

AF:

0.199

Gnomad SAS exome

AF:

0.344

Gnomad FIN exome

AF:

0.167

Gnomad NFE exome

AF:

0.240

Gnomad OTH exome

AF:

0.257

GnomAD4 exome

AF:

0.263

AC:

383536

AN:

1456652

Hom.:

53930

Cov.:

AF XY:

0.265

AC XY:

191797

AN XY:

724456

show subpopulations

Gnomad4 AFR exome

AF:

0.581

Gnomad4 AMR exome

AF:

0.318

Gnomad4 ASJ exome

AF:

0.305

Gnomad4 EAS exome

AF:

0.234

Gnomad4 SAS exome

AF:

0.347

Gnomad4 FIN exome

AF:

0.167

Gnomad4 NFE exome

AF:

0.248

Gnomad4 OTH exome

AF:

0.283

GnomAD4 genome

AF:

0.341

AC:

51732

AN:

151876

Hom.:

10502

Cov.:

AF XY:

0.335

AC XY:

24898

AN XY:

74224

show subpopulations

Gnomad4 AFR

AF:

0.571

Gnomad4 AMR

AF:

0.301

Gnomad4 ASJ

AF:

0.299

Gnomad4 EAS

AF:

0.217

Gnomad4 SAS

AF:

0.334

Gnomad4 FIN

AF:

0.177

Gnomad4 NFE

AF:

0.247

Gnomad4 OTH

AF:

0.331

Alfa

AF:

0.272

Hom.:

14310

Bravo

AF:

0.361

Asia WGS

AF:

0.300

AC:

1044

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Mandibulofacial dysostosis with alopecia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

7.2

DANN

Benign

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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