dbSNP rs7958316: P2RX7:p.Arg276His (chr12-121167570-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_002562.6(P2RX7):c.827G>A(p.Arg276His) variant causes a missense change. The variant allele was found at a frequency of 0.0191 in 1,612,124 control chromosomes in the GnomAD database, including 371 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.016 ( 27 hom., cov: 31)

Exomes 𝑓: 0.019 ( 344 hom. )

Consequence

P2RX7
NM_002562.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.61

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:

LOC105370032 (HGNC:):

LOC105370032 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011648238).

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.016 (2439/152142) while in subpopulation SAS AF= 0.0311 (150/4820). AF 95% confidence interval is 0.0271. There are 27 homozygotes in gnomad4. There are 1249 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RX7	NM_002562.6 link	c.827G>A	p.Arg276His	missense_variant	Exon 8 of 13	ENST00000328963.10	NP_002553.3	Q99572-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P2RX7	ENST00000328963.10 link	c.827G>A	p.Arg276His	missense_variant	Exon 8 of 13	1	NM_002562.6	ENSP00000330696.6		Q99572-1

Frequencies

GnomAD3 genomes

AF:

0.0161

AC:

2441

AN:

152024

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00411

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0218

Gnomad ASJ

AF:

0.0164

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.0311

Gnomad FIN

AF:

0.0279

Gnomad MID

AF:

0.0382

Gnomad NFE

AF:

0.0203

Gnomad OTH

AF:

0.0158

GnomAD3 exomes

AF:

0.0178

AC:

4442

AN:

249296

Hom.:

AF XY:

0.0191

AC XY:

2576

AN XY:

134856

show subpopulations

Gnomad AFR exome

AF:

0.00310

Gnomad AMR exome

AF:

0.0132

Gnomad ASJ exome

AF:

0.0144

Gnomad EAS exome

AF:

0.000825

Gnomad SAS exome

AF:

0.0285

Gnomad FIN exome

AF:

0.0234

Gnomad NFE exome

AF:

0.0203

Gnomad OTH exome

AF:

0.0194

GnomAD4 exome

AF:

0.0194

AC:

28300

AN:

1459982

Hom.:

344

Cov.:

AF XY:

0.0200

AC XY:

14492

AN XY:

726364

show subpopulations

Gnomad4 AFR exome

AF:

0.00297

Gnomad4 AMR exome

AF:

0.0125

Gnomad4 ASJ exome

AF:

0.0144

Gnomad4 EAS exome

AF:

0.000304

Gnomad4 SAS exome

AF:

0.0274

Gnomad4 FIN exome

AF:

0.0212

Gnomad4 NFE exome

AF:

0.0203

Gnomad4 OTH exome

AF:

0.0180

GnomAD4 genome

AF:

0.0160

AC:

2439

AN:

152142

Hom.:

Cov.:

AF XY:

0.0168

AC XY:

1249

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.00410

Gnomad4 AMR

AF:

0.0217

Gnomad4 ASJ

AF:

0.0164

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.0311

Gnomad4 FIN

AF:

0.0279

Gnomad4 NFE

AF:

0.0203

Gnomad4 OTH

AF:

0.0156

Alfa

AF:

0.0189

Hom.:

Bravo

AF:

0.0136

TwinsUK

AF:

0.0202

AC:

ALSPAC

AF:

0.0239

AC:

ESP6500AA

AF:

0.00363

AC:

ESP6500EA

AF:

0.0165

AC:

142

ExAC

AF:

0.0174

AC:

2117

Asia WGS

AF:

0.0140

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.93

MetaRNN

Benign

0.012

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.4

PrimateAI

Benign

0.34

REVEL

Benign

0.14

Sift4G

Benign

0.17

Polyphen

0.95

Vest4

0.095

ClinPred

0.014

GERP RS

6.0

Varity_R

0.10

gMVP

0.65

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