Variant rs73403850 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP3BP4_StrongBP6_Very_StrongBS2

The NM_002562.6(P2RX7):c.959T>C(p.Leu320Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000801 in 1,469,704 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0042 ( 7 hom., cov: 31)

Exomes 𝑓: 0.00041 ( 3 hom. )

Consequence

P2RX7
NM_002562.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.11

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 -15 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 5: AlphaMissense, BayesDel_noAF, Cadd, Eigen, MutationAssessor [when max_spliceai, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.013779283).

BP6

Variant 12-121175465-T-C is Benign according to our data. Variant chr12-121175465-T-C is described in ClinVar as [Benign]. Clinvar id is 716992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
P2RX7	NM_002562.6 linkuse as main transcript	c.959T>C	p.Leu320Pro	missense_variant	9/13	ENST00000328963.10
LOC105370032	XR_001749352.3 linkuse as main transcript	n.327+28033A>G		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.959T>C	p.Leu320Pro	missense_variant	9/13	1	NM_002562.6	P1	Q99572-1

Frequencies

GnomAD3 genomes

AF:

0.00416

AC:

633

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0142

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00117

AC:

293

AN:

251442

Hom.:

AF XY:

0.000817

AC XY:

111

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.0150

Gnomad AMR exome

AF:

0.00121

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000412

AC:

543

AN:

1317442

Hom.:

Cov.:

AF XY:

0.000343

AC XY:

228

AN XY:

663818

show subpopulations

Gnomad4 AFR exome

AF:

0.0135

Gnomad4 AMR exome

AF:

0.00128

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000255

Gnomad4 OTH exome

AF:

0.000845

GnomAD4 genome

AF:

0.00416

AC:

634

AN:

152262

Hom.:

Cov.:

AF XY:

0.00391

AC XY:

291

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0142

Gnomad4 AMR

AF:

0.00229

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.000902

Hom.:

Bravo

AF:

0.00495

ESP6500AA

AF:

0.0152

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00139

AC:

169

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0000546

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Uncertain

0.043

BayesDel_noAF

Pathogenic

0.30

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.40

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.89

MetaRNN

Benign

0.014

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.5

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.72

REVEL

Uncertain

0.33

Sift4G

Uncertain

0.0040

Polyphen

1.0

Vest4

0.92

MVP

0.85

ClinPred

0.090

GERP RS

5.8

Varity_R

0.46

gMVP

0.85

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over