rs10305860

chr4-147484735-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001957.4(EDNRA):c.-70-877G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 152,040 control chromosomes in the GnomAD database, including 12,149 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.38 (12149 hom., cov: 33)
• Consequence: EDNRA NM_001957.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.114

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EDNRA	NM_001957.4	c.-70-877G>A		intron_variant		ENST00000651419.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EDNRA	ENST00000651419.1	c.-70-877G>A		intron_variant			NM_001957.4	P1

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57464 AN: 151920 Hom.: 12126 Cov.: 33

Gnomad AFR AF: 0.578

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.371

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.378 AC: 57538 AN: 152040 Hom.: 12149 Cov.: 33 AF XY: 0.374 AC XY: 27812 AN XY: 74290

Gnomad4 AFR AF: 0.578

Gnomad4 AMR AF: 0.313

Gnomad4 ASJ AF: 0.362

Gnomad4 EAS AF: 0.329

Gnomad4 SAS AF: 0.410

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.296

Gnomad4 OTH AF: 0.370

Alfa AF: 0.319 Hom.: 5331

Bravo AF: 0.393

Asia WGS AF: 0.409 AC: 1422 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.8
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

Other links and lift over

dbSNP: rs10305860; hg19: chr4-148405887; COSMIC: COSV60098447; COSMIC: COSV60098447;