rs1801708

Positions:

• chr4-147481217-G-A
• chr4-147481217-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001957.4(EDNRA):​c.-230G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 152,706 control chromosomes in the GnomAD database, including 20,327 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as protective (no stars).

• Frequency:
  • Genomes: 𝑓 0.46 (20282 hom., cov: 32)
  • Exomes 𝑓: 0.39 (45 hom.)
• Consequence: EDNRA NM_001957.4 5_prime_UTR
• Clinical Significance: protective no assertion criteria provided B:1
• Conservation: PhyloP100: 1.56

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 4-147481217-G-A is Benign according to our data. Variant chr4-147481217-G-A is described in ClinVar as [protective]. Clinvar id is 16642.Status of the report is no_assertion_criteria_provided, 0 stars. We mark this variant Likely_benign, oryginal submission is: [protective].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EDNRA	NM_001957.4	c.-230G>A		5_prime_UTR_variant	1/8	ENST00000651419.1	NP_001948.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EDNRA	ENST00000651419.1	c.-230G>A		5_prime_UTR_variant	1/8		NM_001957.4	ENSP00000498969	P1

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69175 AN: 151974 Hom.: 20229 Cov.: 32

Gnomad AFR AF: 0.841

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.436

GnomAD4 exome AF: 0.390 AC: 240 AN: 616 Hom.: 45 Cov.: 0 AF XY: 0.384 AC XY: 132 AN XY: 344

Gnomad4 AFR exome AF: 0.833

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.333

Gnomad4 SAS exome AF: 0.417

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.299

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.456 AC: 69289 AN: 152090 Hom.: 20282 Cov.: 32 AF XY: 0.449 AC XY: 33403 AN XY: 74340

Gnomad4 AFR AF: 0.841

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.371

Gnomad4 EAS AF: 0.327

Gnomad4 SAS AF: 0.438

Gnomad4 FIN AF: 0.242

Gnomad4 NFE AF: 0.297

Gnomad4 OTH AF: 0.435

Alfa AF: 0.330 Hom.: 9228

Bravo AF: 0.481

Asia WGS AF: 0.439 AC: 1524 AN: 3478

ClinVar

Significance: protective

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Migraine, resistance to Benign:1

protective, no assertion criteria provided

literature only

OMIM

May 22, 2001

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	15
DANN	Benign	0.87

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: rs1801708; hg19: chr4-148402369;