Variant rs3751143 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002562.6(P2RX7):c.1487A>C(p.Glu496Ala) variant causes a missense change. The variant allele was found at a frequency of 0.182 in 1,613,952 control chromosomes in the GnomAD database, including 28,127 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.16 ( 2070 hom., cov: 32)

Exomes 𝑓: 0.18 ( 26057 hom. )

Consequence

P2RX7
NM_002562.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.51

Variant links:

Genes affected

P2RX7 (HGNC:8537): (purinergic receptor P2X 7) The product of this gene belongs to the family of purinoceptors for ATP. This receptor functions as a ligand-gated ion channel and is responsible for ATP-dependent lysis of macrophages through the formation of membrane pores permeable to large molecules. Activation of this nuclear receptor by ATP in the cytoplasm may be a mechanism by which cellular activity can be coupled to changes in gene expression. Multiple alternatively spliced variants have been identified, most of which fit nonsense-mediated decay (NMD) criteria. [provided by RefSeq, Jul 2010]

P2RX7 links:

P2RX7 (HGNC:):

P2RX7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016499162).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P2RX7	NM_002562.6 linkuse as main transcript	c.1487A>C	p.Glu496Ala	missense_variant	13/13	ENST00000328963.10	NP_002553.3	Q99572-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
P2RX7	ENST00000328963.10 linkuse as main transcript	c.1487A>C	p.Glu496Ala	missense_variant	13/13	1	NM_002562.6	ENSP00000330696.6		Q99572-1

Frequencies

GnomAD3 genomes

AF:

0.159

AC:

24107

AN:

152076

Hom.:

2078

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0934

Gnomad AMI

AF:

0.177

Gnomad AMR

AF:

0.179

Gnomad ASJ

AF:

0.198

Gnomad EAS

AF:

0.258

Gnomad SAS

AF:

0.290

Gnomad FIN

AF:

0.102

Gnomad MID

AF:

0.278

Gnomad NFE

AF:

0.181

Gnomad OTH

AF:

0.202

GnomAD3 exomes

AF:

0.189

AC:

47509

AN:

251024

Hom.:

4876

AF XY:

0.197

AC XY:

26682

AN XY:

135708

show subpopulations

Gnomad AFR exome

AF:

0.0886

Gnomad AMR exome

AF:

0.182

Gnomad ASJ exome

AF:

0.201

Gnomad EAS exome

AF:

0.256

Gnomad SAS exome

AF:

0.284

Gnomad FIN exome

AF:

0.105

Gnomad NFE exome

AF:

0.183

Gnomad OTH exome

AF:

0.205

GnomAD4 exome

AF:

0.185

AC:

270026

AN:

1461758

Hom.:

26057

Cov.:

AF XY:

0.189

AC XY:

137326

AN XY:

727178

show subpopulations

Gnomad4 AFR exome

AF:

0.0921

Gnomad4 AMR exome

AF:

0.183

Gnomad4 ASJ exome

AF:

0.193

Gnomad4 EAS exome

AF:

0.274

Gnomad4 SAS exome

AF:

0.281

Gnomad4 FIN exome

AF:

0.108

Gnomad4 NFE exome

AF:

0.180

Gnomad4 OTH exome

AF:

0.189

GnomAD4 genome

AF:

0.158

AC:

24097

AN:

152194

Hom.:

2070

Cov.:

AF XY:

0.159

AC XY:

11860

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.0932

Gnomad4 AMR

AF:

0.178

Gnomad4 ASJ

AF:

0.198

Gnomad4 EAS

AF:

0.258

Gnomad4 SAS

AF:

0.289

Gnomad4 FIN

AF:

0.102

Gnomad4 NFE

AF:

0.181

Gnomad4 OTH

AF:

0.205

Alfa

AF:

0.189

Hom.:

6961

Bravo

AF:

0.160

TwinsUK

AF:

0.171

AC:

633

ALSPAC

AF:

0.170

AC:

657

ESP6500AA

AF:

0.0899

AC:

396

ESP6500EA

AF:

0.185

AC:

1590

ExAC

AF:

0.190

AC:

23012

Asia WGS

AF:

0.274

AC:

951

AN:

3478

EpiCase

AF:

0.194

EpiControl

AF:

0.199

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Uncertain

0.020

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.82

MetaRNN

Benign

0.0016

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.7

PrimateAI

Benign

0.44

REVEL

Benign

0.20

Sift4G

Uncertain

0.0080

Polyphen

0.99

Vest4

0.13

ClinPred

0.011

GERP RS

5.2

Varity_R

0.23

gMVP

0.49

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over