rs7655670

Positions:

• chr4-147502686-T-C
• chr4-147502686-T-G

Variant summary

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

The NM_001957.4(EDNRA):​c.420+16585T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 152,090 control chromosomes in the GnomAD database, including 14,982 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 0.42 (14982 hom., cov: 33)
• Consequence: EDNRA NM_001957.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.401

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EDNRA	NM_001957.4	c.420+16585T>C		intron_variant		ENST00000651419.1	NP_001948.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EDNRA	ENST00000651419.1	c.420+16585T>C		intron_variant			NM_001957.4	ENSP00000498969	P1

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63221 AN: 151972 Hom.: 14958 Cov.: 33

Gnomad AFR AF: 0.657

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.377

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.406

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

GnomAD4 genome AF: 0.416 AC: 63289 AN: 152090 Hom.: 14982 Cov.: 33 AF XY: 0.412 AC XY: 30629 AN XY: 74348

Gnomad4 AFR AF: 0.657

Gnomad4 AMR AF: 0.341

Gnomad4 ASJ AF: 0.377

Gnomad4 EAS AF: 0.305

Gnomad4 SAS AF: 0.455

Gnomad4 FIN AF: 0.265

Gnomad4 NFE AF: 0.318

Gnomad4 OTH AF: 0.405

Alfa AF: 0.275 Hom.: 1175

Bravo AF: 0.431

Asia WGS AF: 0.429 AC: 1490 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.9
DANN	Benign	0.31

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: rs7655670; hg19: chr4-148423838;