4-147540226-G-A

Position:

• chr4-147540226-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001957.4(EDNRA):​c.1035-151G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 766,582 control chromosomes in the GnomAD database, including 35,597 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (12240 hom., cov: 32)
  • Exomes 𝑓: 0.26 (23357 hom.)
• Consequence: EDNRA NM_001957.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.234

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 4-147540226-G-A is Benign according to our data. Variant chr4-147540226-G-A is described in ClinVar as [Benign]. Clinvar id is 1233007.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EDNRA	NM_001957.4	c.1035-151G>A		intron_variant		ENST00000651419.1	NP_001948.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EDNRA	ENST00000651419.1	c.1035-151G>A		intron_variant			NM_001957.4	ENSP00000498969	P1

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54622 AN: 151976 Hom.: 12226 Cov.: 32

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.350

GnomAD4 exome AF: 0.262 AC: 161204 AN: 614488 Hom.: 23357 AF XY: 0.265 AC XY: 84127 AN XY: 317126

Gnomad4 AFR exome AF: 0.634

Gnomad4 AMR exome AF: 0.317

Gnomad4 ASJ exome AF: 0.306

Gnomad4 EAS exome AF: 0.240

Gnomad4 SAS exome AF: 0.347

Gnomad4 FIN exome AF: 0.165

Gnomad4 NFE exome AF: 0.243

Gnomad4 OTH exome AF: 0.288

GnomAD4 genome AF: 0.359 AC: 54672 AN: 152094 Hom.: 12240 Cov.: 32 AF XY: 0.353 AC XY: 26277 AN XY: 74358

Gnomad4 AFR AF: 0.636

Gnomad4 AMR AF: 0.306

Gnomad4 ASJ AF: 0.301

Gnomad4 EAS AF: 0.218

Gnomad4 SAS AF: 0.335

Gnomad4 FIN AF: 0.177

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.346

Alfa AF: 0.291 Hom.: 1518

Bravo AF: 0.382

Asia WGS AF: 0.305 AC: 1062 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 11, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	7.5
DANN	Benign	0.68

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: rs2292765; hg19: chr4-148461378;