Variant 12-121162435-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 1P and 12B. PP3BP4_StrongBS1BS2

The NM_002562.6(P2RX7):c.448G>A(p.Gly150Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0161 in 1,613,846 control chromosomes in the GnomAD database, including 274 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 0.012 ( 15 hom., cov: 32)

Exomes 𝑓: 0.016 ( 259 hom. )

Consequence

P2RX7
NM_002562.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.12

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 -11 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 7: AlphaMissense, BayesDel_noAF, Cadd, Dann, Eigen, MutationAssessor, phyloP100way_vertebrate [when max_spliceai, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.015136242).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0119 (1813/152244) while in subpopulation NFE AF= 0.0181 (1233/68008). AF 95% confidence interval is 0.0173. There are 15 homozygotes in gnomad4. There are 799 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P2RX7	NM_002562.6 linkuse as main transcript	c.448G>A	p.Gly150Arg	missense_variant	5/13	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.448G>A	p.Gly150Arg	missense_variant	5/13	1	NM_002562.6	ENSP00000330696.6		Q99572-1

Frequencies

GnomAD3 genomes

AF:

0.0119

AC:

1814

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00396

Gnomad AMI

AF:

0.0636

Gnomad AMR

AF:

0.00910

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.00424

Gnomad SAS

AF:

0.000830

Gnomad FIN

AF:

0.0131

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0181

Gnomad OTH

AF:

0.00908

GnomAD3 exomes

AF:

0.0121

AC:

3049

AN:

251030

Hom.:

AF XY:

0.0118

AC XY:

1603

AN XY:

135692

show subpopulations

Gnomad AFR exome

AF:

0.00314

Gnomad AMR exome

AF:

0.00868

Gnomad ASJ exome

AF:

0.00973

Gnomad EAS exome

AF:

0.00419

Gnomad SAS exome

AF:

0.00114

Gnomad FIN exome

AF:

0.0115

Gnomad NFE exome

AF:

0.0187

Gnomad OTH exome

AF:

0.0196

GnomAD4 exome

AF:

0.0165

AC:

24093

AN:

1461602

Hom.:

259

Cov.:

AF XY:

0.0160

AC XY:

11606

AN XY:

727106

show subpopulations

Gnomad4 AFR exome

AF:

0.00326

Gnomad4 AMR exome

AF:

0.00866

Gnomad4 ASJ exome

AF:

0.0109

Gnomad4 EAS exome

AF:

0.00239

Gnomad4 SAS exome

AF:

0.00140

Gnomad4 FIN exome

AF:

0.0145

Gnomad4 NFE exome

AF:

0.0193

Gnomad4 OTH exome

AF:

0.0139

GnomAD4 genome

AF:

0.0119

AC:

1813

AN:

152244

Hom.:

Cov.:

AF XY:

0.0107

AC XY:

799

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.00395

Gnomad4 AMR

AF:

0.00902

Gnomad4 ASJ

AF:

0.0101

Gnomad4 EAS

AF:

0.00425

Gnomad4 SAS

AF:

0.000831

Gnomad4 FIN

AF:

0.0131

Gnomad4 NFE

AF:

0.0181

Gnomad4 OTH

AF:

0.00899

Alfa

AF:

0.0159

Hom.:

Bravo

AF:

0.0116

TwinsUK

AF:

0.0167

AC:

ALSPAC

AF:

0.0223

AC:

ESP6500AA

AF:

0.00431

AC:

ESP6500EA

AF:

0.0181

AC:

156

ExAC

AF:

0.0126

AC:

1536

Asia WGS

AF:

0.00808

AC:

AN:

3478

EpiCase

AF:

0.0158

EpiControl

AF:

0.0138

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.74

BayesDel_addAF

Uncertain

0.082

BayesDel_noAF

Pathogenic

0.36

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.50

Eigen

Pathogenic

0.96

Eigen_PC

Pathogenic

0.87

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

MetaRNN

Benign

0.015

MetaSVM

Benign

-0.58

MutationAssessor

Pathogenic

3.6

PrimateAI

Uncertain

0.59

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.36

MutPred

0.35

Gain of catalytic residue at G150 (P = 0.0116);

ClinPred

0.062

GERP RS

5.6

Varity_R

0.37

gMVP

0.94

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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