dbSNP rs1718119: P2RX7:p.Ala348Thr (chr12-121177300-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002562.6(P2RX7):c.1042G>A(p.Ala348Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 1,613,570 control chromosomes in the GnomAD database, including 122,769 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict 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 0.39 ( 11881 hom., cov: 32)

Exomes 𝑓: 0.38 ( 110888 hom. )

Consequence

P2RX7
NM_002562.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.26

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:

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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=0.0015598834).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RX7	NM_002562.6 link	c.1042G>A	p.Ala348Thr	missense_variant	Exon 11 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.1042G>A	p.Ala348Thr	missense_variant	Exon 11 of 13	1	NM_002562.6	ENSP00000330696.6		Q99572-1

Frequencies

GnomAD3 genomes

AF:

0.387

AC:

58849

AN:

151882

Hom.:

11860

Cov.:

show subpopulations

Gnomad AFR

AF:

0.446

Gnomad AMI

AF:

0.391

Gnomad AMR

AF:

0.243

Gnomad ASJ

AF:

0.344

Gnomad EAS

AF:

0.127

Gnomad SAS

AF:

0.367

Gnomad FIN

AF:

0.449

Gnomad MID

AF:

0.278

Gnomad NFE

AF:

0.399

Gnomad OTH

AF:

0.364

GnomAD3 exomes

AF:

0.348

AC:

87591

AN:

251412

Hom.:

16841

AF XY:

0.357

AC XY:

48458

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.459

Gnomad AMR exome

AF:

0.167

Gnomad ASJ exome

AF:

0.350

Gnomad EAS exome

AF:

0.111

Gnomad SAS exome

AF:

0.396

Gnomad FIN exome

AF:

0.452

Gnomad NFE exome

AF:

0.393

Gnomad OTH exome

AF:

0.351

GnomAD4 exome

AF:

0.385

AC:

562475

AN:

1461570

Hom.:

110888

Cov.:

AF XY:

0.386

AC XY:

280359

AN XY:

727098

show subpopulations

Gnomad4 AFR exome

AF:

0.464

Gnomad4 AMR exome

AF:

0.179

Gnomad4 ASJ exome

AF:

0.354

Gnomad4 EAS exome

AF:

0.139

Gnomad4 SAS exome

AF:

0.399

Gnomad4 FIN exome

AF:

0.447

Gnomad4 NFE exome

AF:

0.397

Gnomad4 OTH exome

AF:

0.373

GnomAD4 genome

AF:

0.388

AC:

58916

AN:

152000

Hom.:

11881

Cov.:

AF XY:

0.382

AC XY:

28407

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.447

Gnomad4 AMR

AF:

0.242

Gnomad4 ASJ

AF:

0.344

Gnomad4 EAS

AF:

0.127

Gnomad4 SAS

AF:

0.368

Gnomad4 FIN

AF:

0.449

Gnomad4 NFE

AF:

0.399

Gnomad4 OTH

AF:

0.359

Alfa

AF:

0.382

Hom.:

29605

Bravo

AF:

0.371

TwinsUK

AF:

0.395

AC:

1466

ALSPAC

AF:

0.393

AC:

1514

ESP6500AA

AF:

0.456

AC:

2007

ESP6500EA

AF:

0.397

AC:

3418

ExAC

AF:

0.358

AC:

43474

Asia WGS

AF:

0.267

AC:

929

AN:

3478

EpiCase

AF:

0.397

EpiControl

AF:

0.384

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.42

DEOGEN2

Benign

0.076

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.034

LIST_S2

Benign

0.084

MetaRNN

Benign

0.0016

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-2.1

PrimateAI

Benign

0.43

REVEL

Benign

0.17

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.026

ClinPred

0.0070

GERP RS

5.6

Varity_R

0.046

gMVP

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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