rs2048894

chr4-147530682-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.549-1824G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 152,030 control chromosomes in the GnomAD database, including 10,900 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 0.35 (10900 hom., cov: 32)
• Consequence: EDNRA NM_001957.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0600

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]

LOC124900795 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EDNRA	NM_001957.4	c.549-1824G>A		intron_variant		ENST00000651419.1
LOC124900795	XR_007058311.1	n.167-4150C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EDNRA	ENST00000651419.1	c.549-1824G>A		intron_variant			NM_001957.4	P1

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52538 AN: 151910 Hom.: 10883 Cov.: 32

Gnomad AFR AF: 0.585

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.337

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

GnomAD4 genome AF: 0.346 AC: 52587 AN: 152030 Hom.: 10900 Cov.: 32 AF XY: 0.340 AC XY: 25283 AN XY: 74308

Gnomad4 AFR AF: 0.585

Gnomad4 AMR AF: 0.301

Gnomad4 ASJ AF: 0.304

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.177

Gnomad4 NFE AF: 0.251

Gnomad4 OTH AF: 0.334

Alfa AF: 0.303 Hom.: 2641

Bravo AF: 0.367

Asia WGS AF: 0.303 AC: 1056 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.2
Dann	Benign	0.57

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: rs2048894; hg19: chr4-148451834;