rs701265

Positions:

• chr3-152836568-A-G
• chr3-152836568-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002563.5(P2RY1):​c.786A>G​(p.Val262Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,613,912 control chromosomes in the GnomAD database, including 39,010 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 0.31 (11352 hom., cov: 32)
  • Exomes 𝑓: 0.17 (27658 hom.)
• Consequence: P2RY1 NM_002563.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.964

Genes affected

P2RY1 (HGNC:8539): (purinergic receptor P2Y1) The product of this gene belongs to the family of G-protein coupled receptors. This family has several receptor subtypes with different pharmacological selectivity, which overlaps in some cases, for various adenosine and uridine nucleotides. This receptor functions as a receptor for extracellular ATP and ADP. In platelets binding to ADP leads to mobilization of intracellular calcium ions via activation of phospholipase C, a change in platelet shape, and probably to platelet aggregation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP7: Synonymous conserved (PhyloP=-0.964 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P2RY1	NM_002563.5	c.786A>G	p.Val262Val	synonymous_variant	1/1	ENST00000305097.6	NP_002554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
P2RY1	ENST00000305097.6	c.786A>G	p.Val262Val	synonymous_variant	1/1	6	NM_002563.5	ENSP00000304767.3

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47054 AN: 151976 Hom.: 11313 Cov.: 32

Gnomad AFR AF: 0.676

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.282

GnomAD3 exomes AF: 0.211 AC: 53037 AN: 251444 Hom.: 7914 AF XY: 0.200 AC XY: 27224 AN XY: 135892

Gnomad AFR exome AF: 0.690

Gnomad AMR exome AF: 0.233

Gnomad ASJ exome AF: 0.144

Gnomad EAS exome AF: 0.281

Gnomad SAS exome AF: 0.188

Gnomad FIN exome AF: 0.149

Gnomad NFE exome AF: 0.149

Gnomad OTH exome AF: 0.192

GnomAD4 exome AF: 0.173 AC: 252456 AN: 1461818 Hom.: 27658 Cov.: 34 AF XY: 0.172 AC XY: 125055 AN XY: 727218

Gnomad4 AFR exome AF: 0.694

Gnomad4 AMR exome AF: 0.236

Gnomad4 ASJ exome AF: 0.139

Gnomad4 EAS exome AF: 0.291

Gnomad4 SAS exome AF: 0.187

Gnomad4 FIN exome AF: 0.146

Gnomad4 NFE exome AF: 0.149

Gnomad4 OTH exome AF: 0.202

GnomAD4 genome AF: 0.310 AC: 47147 AN: 152094 Hom.: 11352 Cov.: 32 AF XY: 0.307 AC XY: 22864 AN XY: 74382

Gnomad4 AFR AF: 0.676

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.269

Gnomad4 SAS AF: 0.193

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.282

Alfa AF: 0.177 Hom.: 7747

Bravo AF: 0.337

Asia WGS AF: 0.264 AC: 921 AN: 3478

EpiCase AF: 0.157

EpiControl AF: 0.160

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	6.1
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: rs701265; hg19: chr3-152554357; COSMIC: COSV59309493;