12-121162450-T-C

Variant names:

• chr12-121162450-T-C
• rs208294
• NM_002562.6:c.463T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002562.6(P2RX7):​c.463T>C​(p.Tyr155His) variant causes a missense change. The variant allele was found at a frequency of 0.552 in 1,613,226 control chromosomes in the GnomAD database, including 249,150 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.

• Frequency:
  • Genomes: 𝑓 0.58 (25986 hom., cov: 31)
  • Exomes 𝑓: 0.55 (223164 hom.)
• Consequence: P2RX7 NM_002562.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.55
• Publications: 158 publications found

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]

ENSG00000295862 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.8173456E-4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RX7	NM_002562.6	c.463T>C	p.Tyr155His	missense_variant	Exon 5 of 13	ENST00000328963.10	NP_002553.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P2RX7	ENST00000328963.10	c.463T>C	p.Tyr155His	missense_variant	Exon 5 of 13	1	NM_002562.6	ENSP00000330696.6

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87683 AN: 151836 Hom.: 25929 Cov.: 31

Gnomad AFR AF: 0.698

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.602

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.540

GnomAD2 exomes AF: 0.512 AC: 128478 AN: 250878 AF XY: 0.514

Gnomad AFR exome AF: 0.698

Gnomad AMR exome AF: 0.303

Gnomad ASJ exome AF: 0.525

Gnomad EAS exome AF: 0.397

Gnomad FIN exome AF: 0.608

Gnomad NFE exome AF: 0.553

Gnomad OTH exome AF: 0.520

GnomAD4 exome AF: 0.549 AC: 801981 AN: 1461272 Hom.: 223164 Cov.: 42 AF XY: 0.547 AC XY: 397489 AN XY: 726934

African (AFR) AF: 0.702 AC: 23497 AN: 33476

American (AMR) AF: 0.319 AC: 14250 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 13841 AN: 26134

East Asian (EAS) AF: 0.418 AC: 16589 AN: 39684

South Asian (SAS) AF: 0.496 AC: 42744 AN: 86244

European-Finnish (FIN) AF: 0.609 AC: 32388 AN: 53190

Middle Eastern (MID) AF: 0.465 AC: 2684 AN: 5766

European-Non Finnish (NFE) AF: 0.560 AC: 622894 AN: 1111694

Other (OTH) AF: 0.548 AC: 33094 AN: 60376

GnomAD4 genome AF: 0.578 AC: 87804 AN: 151954 Hom.: 25986 Cov.: 31 AF XY: 0.572 AC XY: 42463 AN XY: 74250

African (AFR) AF: 0.699 AC: 28971 AN: 41464

American (AMR) AF: 0.427 AC: 6517 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.537 AC: 1863 AN: 3470

East Asian (EAS) AF: 0.406 AC: 2094 AN: 5156

South Asian (SAS) AF: 0.497 AC: 2393 AN: 4818

European-Finnish (FIN) AF: 0.602 AC: 6348 AN: 10546

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.558 AC: 37912 AN: 67924

Other (OTH) AF: 0.539 AC: 1138 AN: 2110

Alfa AF: 0.548 Hom.: 57351

Bravo AF: 0.568

ESP6500AA AF: 0.691 AC: 3046

ESP6500EA AF: 0.554 AC: 4761

ExAC AF: 0.523 AC: 63531

Asia WGS AF: 0.475 AC: 1653 AN: 3478

EpiCase AF: 0.554

EpiControl AF: 0.545

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.12
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.51	T
MetaRNN	Benign	0.00018	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		6.5
PrimateAI	Uncertain	0.57	T
Sift4G	Uncertain	0.054	T
Polyphen		1.0	D
Vest4		0.22
ClinPred		0.037	T
GERP RS		5.6
Varity_R		0.19
gMVP		0.77
Mutation Taster		=96/4	polymorphism (auto)

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

Other links and lift over

dbSNP: rs208294; hg19: chr12-121600253; COSMIC: COSV55855244; COSMIC: COSV55855244;