rs2230913

Positions:

• chr12-121184577-C-G
• chr12-121184577-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002562.6(P2RX7):​c.1563C>G​(p.His521Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0071 in 1,614,104 control chromosomes in the GnomAD database, including 728 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 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 0.038 (366 hom., cov: 33)
  • Exomes 𝑓: 0.0039 (362 hom.)
• Consequence: P2RX7 NM_002562.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.05

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014154017).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P2RX7	NM_002562.6	c.1563C>G	p.His521Gln	missense_variant	13/13	ENST00000328963.10	NP_002553.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
P2RX7	ENST00000328963.10	c.1563C>G	p.His521Gln	missense_variant	13/13	1	NM_002562.6	ENSP00000330696.6

Frequencies

GnomAD3 genomes AF: 0.0375 AC: 5709 AN: 152212 Hom.: 360 Cov.: 33

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0133

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.0258

GnomAD3 exomes AF: 0.0102 AC: 2554 AN: 250558 Hom.: 156 AF XY: 0.00751 AC XY: 1019 AN XY: 135618

Gnomad AFR exome AF: 0.139

Gnomad AMR exome AF: 0.00651

Gnomad ASJ exome AF: 0.000897

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000459

Gnomad OTH exome AF: 0.00474

GnomAD4 exome AF: 0.00391 AC: 5719 AN: 1461774 Hom.: 362 Cov.: 40 AF XY: 0.00344 AC XY: 2499 AN XY: 727186

Gnomad4 AFR exome AF: 0.135

Gnomad4 AMR exome AF: 0.00783

Gnomad4 ASJ exome AF: 0.000804

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000255

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000239

Gnomad4 OTH exome AF: 0.00841

GnomAD4 genome AF: 0.0377 AC: 5741 AN: 152330 Hom.: 366 Cov.: 33 AF XY: 0.0361 AC XY: 2693 AN XY: 74498

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.0133

Gnomad4 ASJ AF: 0.00230

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000367

Gnomad4 OTH AF: 0.0255

Alfa AF: 0.00217 Hom.: 7

Bravo AF: 0.0434

ESP6500AA AF: 0.140 AC: 615

ESP6500EA AF: 0.000814 AC: 7

ExAC AF: 0.0128 AC: 1552

Asia WGS AF: 0.00953 AC: 33 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000534

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.0010
DANN	Benign	0.55
DEOGEN2	Benign	0.068	T
Eigen	Benign	-2.4
Eigen_PC	Benign	-2.5
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.36	T
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.29	T
REVEL	Benign	0.054
Sift4G	Benign	0.55	T
Polyphen		0.0	B
Vest4		0.030
MutPred		0.12		Loss of catalytic residue at L523 (P = 0.1094);
ClinPred		0.0060	T
GERP RS		-10
Varity_R		0.029
gMVP		0.19

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

Other links and lift over

dbSNP: rs2230913; hg19: chr12-121622380;