Variant chr12-121156133-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002562.6(P2RX7):c.349C>T(p.Arg117Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00191 in 1,613,974 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 8 hom. )

Consequence

P2RX7
NM_002562.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0990

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013349801).

BP6

Variant 12-121156133-C-T is Benign according to our data. Variant chr12-121156133-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2643404.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
P2RX7	NM_002562.6 linkuse as main transcript	c.349C>T	p.Arg117Trp	missense_variant	3/13	ENST00000328963.10
LOC105370032	XR_001749352.3 linkuse as main transcript	n.328-29292G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
P2RX7	ENST00000328963.10 linkuse as main transcript	c.349C>T	p.Arg117Trp	missense_variant	3/13	1	NM_002562.6	P1	Q99572-1

Frequencies

GnomAD3 genomes

AF:

0.00144

AC:

219

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00254

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00128

AC:

322

AN:

251422

Hom.:

AF XY:

0.00126

AC XY:

171

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.00113

Gnomad ASJ exome

AF:

0.000893

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00219

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00196

AC:

2862

AN:

1461644

Hom.:

Cov.:

AF XY:

0.00195

AC XY:

1421

AN XY:

727138

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.00127

Gnomad4 ASJ exome

AF:

0.000689

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000232

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.00236

Gnomad4 OTH exome

AF:

0.00187

GnomAD4 genome

AF:

0.00143

AC:

218

AN:

152330

Hom.:

Cov.:

AF XY:

0.00134

AC XY:

100

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.000529

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00253

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00209

Hom.:

Bravo

AF:

0.00159

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00198

AC:

ExAC

AF:

0.00126

AC:

153

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00311

EpiControl

AF:

0.00231

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2022

P2RX7: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Benign

0.18

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.67

M_CAP

Benign

0.014

MetaRNN

Benign

0.013

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.69

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.25

Sift4G

Pathogenic

0.0010

Polyphen

0.92

Vest4

0.45

MVP

0.40

ClinPred

0.039

GERP RS

-1.2

Varity_R

0.075

gMVP

0.67

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over