NM_002562.6:c.462G>A

Variant names:

• chr12-121162449-G-A
• rs28360448
• NM_002562.6:c.462G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002562.6(P2RX7):​c.462G>A​(p.Val154Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0138 in 1,613,892 control chromosomes in the GnomAD database, including 744 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 0.038 (290 hom., cov: 32)
  • Exomes 𝑓: 0.011 (454 hom.)
• Consequence: P2RX7 NM_002562.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.43
• Publications: 0 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP7: Synonymous conserved (PhyloP=-2.43 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002562.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RX7	NM_002562.6	MANE Select	c.462G>A	p.Val154Val	synonymous	Exon 5 of 13	NP_002553.3
	P2RX7	NR_033948.2		n.696G>A		non_coding_transcript_exon	Exon 6 of 13
	P2RX7	NR_033949.2		n.696G>A		non_coding_transcript_exon	Exon 6 of 14

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RX7	ENST00000328963.10	TSL:1 MANE Select	c.462G>A	p.Val154Val	synonymous	Exon 5 of 13	ENSP00000330696.6	Q99572-1
	P2RX7	ENST00000538011.5	TSL:1	n.*217G>A		non_coding_transcript_exon	Exon 6 of 14	ENSP00000439247.1	F5H2X6
	P2RX7	ENST00000541022.5	TSL:1	n.*2G>A		non_coding_transcript_exon	Exon 4 of 11	ENSP00000441230.1	Q99572-3

Frequencies

GnomAD3 genomes AF: 0.0383 AC: 5819 AN: 152110 Hom.: 291 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0141

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0472

Gnomad FIN AF: 0.0107

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00556

Gnomad OTH AF: 0.0330

GnomAD2 exomes AF: 0.0185 AC: 4645 AN: 251112 AF XY: 0.0183

Gnomad AFR exome AF: 0.120

Gnomad AMR exome AF: 0.00900

Gnomad ASJ exome AF: 0.00645

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00865

Gnomad NFE exome AF: 0.00570

Gnomad OTH exome AF: 0.0148

GnomAD4 exome AF: 0.0112 AC: 16374 AN: 1461662 Hom.: 454 Cov.: 33 AF XY: 0.0120 AC XY: 8710 AN XY: 727122

African (AFR) AF: 0.125 AC: 4169 AN: 33478

American (AMR) AF: 0.00961 AC: 430 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00624 AC: 163 AN: 26134

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39700

South Asian (SAS) AF: 0.0441 AC: 3807 AN: 86250

European-Finnish (FIN) AF: 0.00777 AC: 414 AN: 53248

Middle Eastern (MID) AF: 0.0238 AC: 137 AN: 5768

European-Non Finnish (NFE) AF: 0.00566 AC: 6289 AN: 1111972

Other (OTH) AF: 0.0159 AC: 962 AN: 60390

GnomAD4 genome AF: 0.0382 AC: 5821 AN: 152230 Hom.: 290 Cov.: 32 AF XY: 0.0375 AC XY: 2789 AN XY: 74438

African (AFR) AF: 0.115 AC: 4793 AN: 41516

American (AMR) AF: 0.0141 AC: 215 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00432 AC: 15 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5184

South Asian (SAS) AF: 0.0466 AC: 225 AN: 4828

European-Finnish (FIN) AF: 0.0107 AC: 113 AN: 10610

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.00556 AC: 378 AN: 68016

Other (OTH) AF: 0.0326 AC: 69 AN: 2114

Alfa AF: 0.0253 Hom.: 87

Bravo AF: 0.0417

Asia WGS AF: 0.0270 AC: 93 AN: 3478

EpiCase AF: 0.00627

EpiControl AF: 0.00622

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.22
DANN	Benign	0.66
PhyloP100		-2.4
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs28360448; hg19: chr12-121600252; COSMIC: COSV107240864; COSMIC: COSV107240864;