3-152835839-C-T

Position:

• chr3-152835839-C-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.57C>T​(p.Ala19Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0523 in 1,612,502 control chromosomes in the GnomAD database, including 3,282 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 0.083 (788 hom., cov: 32)
  • Exomes 𝑓: 0.049 (2494 hom.)
• Consequence: P2RY1 NM_002563.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.260

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=-0.69).
• BP7: Synonymous conserved (PhyloP=-0.26 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P2RY1	NM_002563.5	c.57C>T	p.Ala19Ala	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.57C>T	p.Ala19Ala	synonymous_variant	1/1	6	NM_002563.5	ENSP00000304767.3

Frequencies

GnomAD3 genomes AF: 0.0833 AC: 12671 AN: 152140 Hom.: 787 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.0698

Gnomad ASJ AF: 0.0303

Gnomad EAS AF: 0.0339

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.0666

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0404

Gnomad OTH AF: 0.0723

GnomAD3 exomes AF: 0.0616 AC: 15378 AN: 249778 Hom.: 681 AF XY: 0.0618 AC XY: 8376 AN XY: 135436

Gnomad AFR exome AF: 0.169

Gnomad AMR exome AF: 0.0575

Gnomad ASJ exome AF: 0.0337

Gnomad EAS exome AF: 0.0382

Gnomad SAS exome AF: 0.109

Gnomad FIN exome AF: 0.0673

Gnomad NFE exome AF: 0.0403

Gnomad OTH exome AF: 0.0528

GnomAD4 exome AF: 0.0491 AC: 71634 AN: 1460244 Hom.: 2494 Cov.: 32 AF XY: 0.0502 AC XY: 36490 AN XY: 726472

Gnomad4 AFR exome AF: 0.170

Gnomad4 AMR exome AF: 0.0598

Gnomad4 ASJ exome AF: 0.0319

Gnomad4 EAS exome AF: 0.0620

Gnomad4 SAS exome AF: 0.107

Gnomad4 FIN exome AF: 0.0636

Gnomad4 NFE exome AF: 0.0395

Gnomad4 OTH exome AF: 0.0551

GnomAD4 genome AF: 0.0834 AC: 12703 AN: 152258 Hom.: 788 Cov.: 32 AF XY: 0.0844 AC XY: 6286 AN XY: 74456

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.0698

Gnomad4 ASJ AF: 0.0303

Gnomad4 EAS AF: 0.0338

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.0666

Gnomad4 NFE AF: 0.0404

Gnomad4 OTH AF: 0.0711

Alfa AF: 0.0438 Hom.: 143

Bravo AF: 0.0859

Asia WGS AF: 0.0860 AC: 302 AN: 3478

EpiCase AF: 0.0403

EpiControl AF: 0.0402

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	7.6
DANN	Benign	0.94
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1065776; hg19: chr3-152553628; COSMIC: COSV59310103;