Genetic Variant P2RY1:p.Ala19Ala (chr3-152835839-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.260

Publications

32 publications found

Variant links:

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]

P2RY1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
P2RY1	NM_002563.5 link	c.57C>T	p.Ala19Ala	synonymous_variant	Exon 1 of 1	ENST00000305097.6	NP_002554.1	P47900

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P2RY1	ENST00000305097.6 link	c.57C>T	p.Ala19Ala	synonymous_variant	Exon 1 of 1	6	NM_002563.5	ENSP00000304767.3		P47900

Frequencies

GnomAD3 genomes

AF:

0.0833

AC:

12671

AN:

152140

Hom.:

787

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.0616

AC:

15378

AN:

249778

AF XY:

0.0618

show subpopulations

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 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.:

AF XY:

0.0502

AC XY:

36490

AN XY:

726472

show subpopulations

African (AFR)

AF:

0.170

AC:

5688

AN:

33456

American (AMR)

AF:

0.0598

AC:

2672

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.0319

AC:

835

AN:

26136

East Asian (EAS)

AF:

0.0620

AC:

2462

AN:

39698

South Asian (SAS)

AF:

0.107

AC:

9202

AN:

86208

European-Finnish (FIN)

AF:

0.0636

AC:

3347

AN:

52620

Middle Eastern (MID)

AF:

0.0443

AC:

228

AN:

5144

European-Non Finnish (NFE)

AF:

0.0395

AC:

43878

AN:

1111944

Other (OTH)

AF:

0.0551

AC:

3322

AN:

60324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

3850

7699

11549

15398

19248

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1824

3648

5472

7296

9120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0834

AC:

12703

AN:

152258

Hom.:

788

Cov.:

AF XY:

0.0844

AC XY:

6286

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.171

AC:

7122

AN:

41542

American (AMR)

AF:

0.0698

AC:

1068

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0303

AC:

105

AN:

3470

East Asian (EAS)

AF:

0.0338

AC:

175

AN:

5174

South Asian (SAS)

AF:

0.112

AC:

540

AN:

4824

European-Finnish (FIN)

AF:

0.0666

AC:

707

AN:

10618

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0404

AC:

2747

AN:

68014

Other (OTH)

AF:

0.0711

AC:

150

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

591

1181

1772

2362

2953

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

276

414

552

690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0444

Hom.:

412

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

(source)

DANN

Benign

0.94

PhyloP100

-0.26

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over