Variant rs3732764 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000302632.4(P2RY12):c.-180+16902G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 1,583,232 control chromosomes in the GnomAD database, including 386,758 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.75 ( 43645 hom., cov: 32)

Exomes 𝑓: 0.69 ( 343113 hom. )

Consequence

P2RY12
ENST00000302632.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.82

Variant links:

Genes affected

MED12L (HGNC:16050): (mediator complex subunit 12L) The protein encoded by this gene is part of the Mediator complex, which is involved in transcriptional coactivation of nearly all RNA polymerase II-dependent genes. The Mediator complex links gene-specific transcriptional activators with the basal transcription machinery. [provided by RefSeq, May 2010]

MED12L links:

P2RY12 (HGNC:18124): (purinergic receptor P2Y12) 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 is involved in platelet aggregation, and is a potential target for the treatment of thromboembolisms and other clotting disorders. Mutations in this gene are implicated in bleeding disorder, platelet type 8 (BDPLT8). Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, Jul 2013]

P2RY12 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BP6

Variant 3-151367790-C-A is Benign according to our data. Variant chr3-151367790-C-A is described in ClinVar as [Benign]. Clinvar id is 1321165.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MED12L	NM_001393769.1 linkuse as main transcript	c.3448+24C>A		intron_variant		ENST00000687756.1	NP_001380698.1
P2RY12	NM_022788.5 linkuse as main transcript	c.-180+16902G>T		intron_variant		ENST00000302632.4	NP_073625.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
P2RY12	ENST00000302632.4 linkuse as main transcript	c.-180+16902G>T		intron_variant		1	NM_022788.5	ENSP00000307259	P1
MED12L	ENST00000687756.1 linkuse as main transcript	c.3448+24C>A		intron_variant			NM_001393769.1	ENSP00000508695	A2

Frequencies

GnomAD3 genomes

AF:

0.751

AC:

114163

AN:

152004

Hom.:

43594

Cov.:

show subpopulations

Gnomad AFR

AF:

0.888

Gnomad AMI

AF:

0.684

Gnomad AMR

AF:

0.761

Gnomad ASJ

AF:

0.692

Gnomad EAS

AF:

0.848

Gnomad SAS

AF:

0.842

Gnomad FIN

AF:

0.684

Gnomad MID

AF:

0.778

Gnomad NFE

AF:

0.666

Gnomad OTH

AF:

0.764

GnomAD3 exomes

AF:

0.736

AC:

173019

AN:

235172

Hom.:

64574

AF XY:

0.733

AC XY:

93232

AN XY:

127154

show subpopulations

Gnomad AFR exome

AF:

0.890

Gnomad AMR exome

AF:

0.808

Gnomad ASJ exome

AF:

0.704

Gnomad EAS exome

AF:

0.841

Gnomad SAS exome

AF:

0.832

Gnomad FIN exome

AF:

0.683

Gnomad NFE exome

AF:

0.664

Gnomad OTH exome

AF:

0.719

GnomAD4 exome

AF:

0.689

AC:

986152

AN:

1431112

Hom.:

343113

Cov.:

AF XY:

0.694

AC XY:

491323

AN XY:

708460

show subpopulations

Gnomad4 AFR exome

AF:

0.897

Gnomad4 AMR exome

AF:

0.803

Gnomad4 ASJ exome

AF:

0.700

Gnomad4 EAS exome

AF:

0.837

Gnomad4 SAS exome

AF:

0.831

Gnomad4 FIN exome

AF:

0.677

Gnomad4 NFE exome

AF:

0.661

Gnomad4 OTH exome

AF:

0.714

GnomAD4 genome

AF:

0.751

AC:

114275

AN:

152120

Hom.:

43645

Cov.:

AF XY:

0.756

AC XY:

56214

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.888

Gnomad4 AMR

AF:

0.761

Gnomad4 ASJ

AF:

0.692

Gnomad4 EAS

AF:

0.849

Gnomad4 SAS

AF:

0.842

Gnomad4 FIN

AF:

0.684

Gnomad4 NFE

AF:

0.666

Gnomad4 OTH

AF:

0.761

Alfa

AF:

0.679

Hom.:

5444

Bravo

AF:

0.762

Asia WGS

AF:

0.814

AC:

2833

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Nizon-Isidor syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.021

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over