Genetic Variant EDNRA:c.1034+19G>A (chr4-147539969-G-A) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001957.4(EDNRA):c.1034+19G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00332 in 1,560,856 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0032 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0033 ( 8 hom. )

Consequence

EDNRA
NM_001957.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.507

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:

LOC124900795 (HGNC:):

LOC124900795 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 4-147539969-G-A is Benign according to our data. Variant chr4-147539969-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1654745.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 492 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDNRA	NM_001957.4 link	c.1034+19G>A		intron_variant	Intron 6 of 7	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.1034+19G>A		intron_variant	Intron 6 of 7		NM_001957.4	ENSP00000498969.1		P25101-1

Frequencies

GnomAD3 genomes

AF:

0.00324

AC:

492

AN:

152046

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000797

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00328

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.00208

Gnomad FIN

AF:

0.00397

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00516

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00241

AC:

505

AN:

209670

Hom.:

AF XY:

0.00239

AC XY:

273

AN XY:

114314

show subpopulations

Gnomad AFR exome

AF:

0.000990

Gnomad AMR exome

AF:

0.00129

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000126

Gnomad SAS exome

AF:

0.00148

Gnomad FIN exome

AF:

0.00201

Gnomad NFE exome

AF:

0.00369

Gnomad OTH exome

AF:

0.00187

GnomAD4 exome

AF:

0.00333

AC:

4690

AN:

1408692

Hom.:

Cov.:

AF XY:

0.00328

AC XY:

2291

AN XY:

698176

show subpopulations

Gnomad4 AFR exome

AF:

0.000790

Gnomad4 AMR exome

AF:

0.00134

Gnomad4 ASJ exome

AF:

0.0000857

Gnomad4 EAS exome

AF:

0.0000511

Gnomad4 SAS exome

AF:

0.00182

Gnomad4 FIN exome

AF:

0.00188

Gnomad4 NFE exome

AF:

0.00385

Gnomad4 OTH exome

AF:

0.00290

GnomAD4 genome

AF:

0.00323

AC:

492

AN:

152164

Hom.:

Cov.:

AF XY:

0.00344

AC XY:

256

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.000795

Gnomad4 AMR

AF:

0.00327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.00208

Gnomad4 FIN

AF:

0.00397

Gnomad4 NFE

AF:

0.00516

Gnomad4 OTH

AF:

0.00143

Alfa

AF:

0.00272

Hom.:

Bravo

AF:

0.00252

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 11, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Migraine with or without aura, susceptibility to, 1;C4225349:Mandibulofacial dysostosis with alopecia

Benign:1

Aug 17, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Likely 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

-0.92

CADD

Benign

0.013

DANN

Benign

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