rs3751143

Variant summary

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

The ENST00000328963.10(P2RX7):ā€‹c.1487A>Cā€‹(p.Glu496Ala) variant causes a missense change. The variant allele was found at a frequency of 0.182 in 1,613,952 control chromosomes in the GnomAD database, including 28,127 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 same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: š‘“ 0.16 ( 2070 hom., cov: 32)
Exomes š‘“: 0.18 ( 26057 hom. )

Consequence

P2RX7
ENST00000328963.10 missense

Scores

2
5
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.51
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]

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=0.0016499162).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
P2RX7NM_002562.6 linkuse as main transcriptc.1487A>C p.Glu496Ala missense_variant 13/13 ENST00000328963.10 NP_002553.3
LOC105370032XR_001749352.3 linkuse as main transcriptn.327+18997T>G intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
P2RX7ENST00000328963.10 linkuse as main transcriptc.1487A>C p.Glu496Ala missense_variant 13/131 NM_002562.6 ENSP00000330696 P1Q99572-1
ENST00000652651.1 linkuse as main transcriptn.3548+1700T>G intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.159
AC:
24107
AN:
152076
Hom.:
2078
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0934
Gnomad AMI
AF:
0.177
Gnomad AMR
AF:
0.179
Gnomad ASJ
AF:
0.198
Gnomad EAS
AF:
0.258
Gnomad SAS
AF:
0.290
Gnomad FIN
AF:
0.102
Gnomad MID
AF:
0.278
Gnomad NFE
AF:
0.181
Gnomad OTH
AF:
0.202
GnomAD3 exomes
AF:
0.189
AC:
47509
AN:
251024
Hom.:
4876
AF XY:
0.197
AC XY:
26682
AN XY:
135708
show subpopulations
Gnomad AFR exome
AF:
0.0886
Gnomad AMR exome
AF:
0.182
Gnomad ASJ exome
AF:
0.201
Gnomad EAS exome
AF:
0.256
Gnomad SAS exome
AF:
0.284
Gnomad FIN exome
AF:
0.105
Gnomad NFE exome
AF:
0.183
Gnomad OTH exome
AF:
0.205
GnomAD4 exome
AF:
0.185
AC:
270026
AN:
1461758
Hom.:
26057
Cov.:
61
AF XY:
0.189
AC XY:
137326
AN XY:
727178
show subpopulations
Gnomad4 AFR exome
AF:
0.0921
Gnomad4 AMR exome
AF:
0.183
Gnomad4 ASJ exome
AF:
0.193
Gnomad4 EAS exome
AF:
0.274
Gnomad4 SAS exome
AF:
0.281
Gnomad4 FIN exome
AF:
0.108
Gnomad4 NFE exome
AF:
0.180
Gnomad4 OTH exome
AF:
0.189
GnomAD4 genome
AF:
0.158
AC:
24097
AN:
152194
Hom.:
2070
Cov.:
32
AF XY:
0.159
AC XY:
11860
AN XY:
74396
show subpopulations
Gnomad4 AFR
AF:
0.0932
Gnomad4 AMR
AF:
0.178
Gnomad4 ASJ
AF:
0.198
Gnomad4 EAS
AF:
0.258
Gnomad4 SAS
AF:
0.289
Gnomad4 FIN
AF:
0.102
Gnomad4 NFE
AF:
0.181
Gnomad4 OTH
AF:
0.205
Alfa
AF:
0.189
Hom.:
6961
Bravo
AF:
0.160
TwinsUK
AF:
0.171
AC:
633
ALSPAC
AF:
0.170
AC:
657
ESP6500AA
AF:
0.0899
AC:
396
ESP6500EA
AF:
0.185
AC:
1590
ExAC
AF:
0.190
AC:
23012
Asia WGS
AF:
0.274
AC:
951
AN:
3478
EpiCase
AF:
0.194
EpiControl
AF:
0.199

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.26
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Uncertain
0.020
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.21
T
Eigen
Pathogenic
0.72
Eigen_PC
Pathogenic
0.69
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.82
T
MetaRNN
Benign
0.0016
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.7
M
MutationTaster
Benign
0.061
P;P;P;P
PrimateAI
Benign
0.44
T
REVEL
Benign
0.20
Sift4G
Uncertain
0.0080
D
Polyphen
0.99
D
Vest4
0.13
ClinPred
0.011
T
GERP RS
5.2
Varity_R
0.23
gMVP
0.49

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.

Other links and lift over

dbSNP: rs3751143; hg19: chr12-121622304; COSMIC: COSV55853761; API