Variant rs2230912 details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000328963.10(P2RX7):c.1379A>G(p.Gln460Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,613,940 control chromosomes in the GnomAD database, including 20,186 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 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 same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.12 ( 1306 hom., cov: 32)

Exomes 𝑓: 0.16 ( 18880 hom. )

Consequence

P2RX7
ENST00000328963.10 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.30

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:

(HGNC:):

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=0.0016370714).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.165 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.1379A>G	p.Gln460Arg	missense_variant	13/13	ENST00000328963.10	NP_002553.3
LOC105370032	XR_001749352.3 linkuse as main transcript	n.327+19105T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
P2RX7	ENST00000328963.10 linkuse as main transcript	c.1379A>G	p.Gln460Arg	missense_variant	13/13	1	NM_002562.6	ENSP00000330696	P1	Q99572-1
	ENST00000652651.1 linkuse as main transcript	n.3548+1808T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.118

AC:

17985

AN:

152014

Hom.:

1308

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0492

Gnomad AMI

AF:

0.123

Gnomad AMR

AF:

0.0799

Gnomad ASJ

AF:

0.165

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.141

Gnomad FIN

AF:

0.162

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.167

Gnomad OTH

AF:

0.114

GnomAD3 exomes

AF:

0.130

AC:

32655

AN:

251306

Hom.:

2555

AF XY:

0.138

AC XY:

18692

AN XY:

135828

show subpopulations

Gnomad AFR exome

AF:

0.0514

Gnomad AMR exome

AF:

0.0581

Gnomad ASJ exome

AF:

0.167

Gnomad EAS exome

AF:

0.000435

Gnomad SAS exome

AF:

0.161

Gnomad FIN exome

AF:

0.163

Gnomad NFE exome

AF:

0.166

Gnomad OTH exome

AF:

0.130

GnomAD4 exome

AF:

0.156

AC:

227374

AN:

1461808

Hom.:

18880

Cov.:

AF XY:

0.156

AC XY:

113436

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.0501

Gnomad4 AMR exome

AF:

0.0608

Gnomad4 ASJ exome

AF:

0.170

Gnomad4 EAS exome

AF:

0.000453

Gnomad4 SAS exome

AF:

0.163

Gnomad4 FIN exome

AF:

0.157

Gnomad4 NFE exome

AF:

0.168

Gnomad4 OTH exome

AF:

0.144

GnomAD4 genome

AF:

0.118

AC:

17987

AN:

152132

Hom.:

1306

Cov.:

AF XY:

0.116

AC XY:

8659

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.0493

Gnomad4 AMR

AF:

0.0798

Gnomad4 ASJ

AF:

0.165

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.141

Gnomad4 FIN

AF:

0.162

Gnomad4 NFE

AF:

0.167

Gnomad4 OTH

AF:

0.112

Alfa

AF:

0.156

Hom.:

4895

Bravo

AF:

0.108

TwinsUK

AF:

0.167

AC:

621

ALSPAC

AF:

0.164

AC:

633

ESP6500AA

AF:

0.0527

AC:

232

ESP6500EA

AF:

0.166

AC:

1429

ExAC

AF:

0.132

AC:

15978

Asia WGS

AF:

0.0640

AC:

224

AN:

3478

EpiCase

AF:

0.169

EpiControl

AF:

0.164

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.090

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.13

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.56

MetaRNN

Benign

0.0016

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

0.95

P;P;P;P

PrimateAI

Benign

0.32

REVEL

Benign

0.22

Sift4G

Benign

0.41

Polyphen

0.0030

Vest4

0.021

ClinPred

0.011

GERP RS

5.2

Varity_R

0.065

gMVP

0.24

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