12-121177300-G-A

Variant names:

• chr12-121177300-G-A
• rs1718119
• NM_002562.6:c.1042G>A

Variant summary

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

The NM_002562.6(P2RX7):​c.1042G>A​(p.Ala348Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 1,613,570 control chromosomes in the GnomAD database, including 122,769 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.39 (11881 hom., cov: 32)
  • Exomes 𝑓: 0.38 (110888 hom.)
• Consequence: P2RX7 NM_002562.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26
• Publications: 178 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=0.0015598834).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.441 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RX7	NM_002562.6	MANE Select	c.1042G>A	p.Ala348Thr	missense	Exon 11 of 13	NP_002553.3
	P2RX7	NR_033948.2		n.1360G>A		non_coding_transcript_exon	Exon 11 of 13
	P2RX7	NR_033949.2		n.1276G>A		non_coding_transcript_exon	Exon 12 of 14

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RX7	ENST00000328963.10	TSL:1 MANE Select	c.1042G>A	p.Ala348Thr	missense	Exon 11 of 13	ENSP00000330696.6
	P2RX7	ENST00000261826.10	TSL:1	n.*495G>A		non_coding_transcript_exon	Exon 10 of 12	ENSP00000261826.6
	P2RX7	ENST00000538011.5	TSL:1	n.*797G>A		non_coding_transcript_exon	Exon 12 of 14	ENSP00000439247.1

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58849 AN: 151882 Hom.: 11860 Cov.: 32

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.364

GnomAD2 exomes AF: 0.348 AC: 87591 AN: 251412 AF XY: 0.357

Gnomad AFR exome AF: 0.459

Gnomad AMR exome AF: 0.167

Gnomad ASJ exome AF: 0.350

Gnomad EAS exome AF: 0.111

Gnomad FIN exome AF: 0.452

Gnomad NFE exome AF: 0.393

Gnomad OTH exome AF: 0.351

GnomAD4 exome AF: 0.385 AC: 562475 AN: 1461570 Hom.: 110888 Cov.: 46 AF XY: 0.386 AC XY: 280359 AN XY: 727098

African (AFR) AF: 0.464 AC: 15523 AN: 33474

American (AMR) AF: 0.179 AC: 8014 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 9247 AN: 26134

East Asian (EAS) AF: 0.139 AC: 5516 AN: 39692

South Asian (SAS) AF: 0.399 AC: 34424 AN: 86250

European-Finnish (FIN) AF: 0.447 AC: 23856 AN: 53414

Middle Eastern (MID) AF: 0.361 AC: 2042 AN: 5664

European-Non Finnish (NFE) AF: 0.397 AC: 441310 AN: 1111838

Other (OTH) AF: 0.373 AC: 22543 AN: 60380

GnomAD4 genome AF: 0.388 AC: 58916 AN: 152000 Hom.: 11881 Cov.: 32 AF XY: 0.382 AC XY: 28407 AN XY: 74280

African (AFR) AF: 0.447 AC: 18521 AN: 41452

American (AMR) AF: 0.242 AC: 3699 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1193 AN: 3470

East Asian (EAS) AF: 0.127 AC: 656 AN: 5180

South Asian (SAS) AF: 0.368 AC: 1774 AN: 4820

European-Finnish (FIN) AF: 0.449 AC: 4729 AN: 10534

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.399 AC: 27144 AN: 67966

Other (OTH) AF: 0.359 AC: 757 AN: 2108

Alfa AF: 0.386 Hom.: 56335

Bravo AF: 0.371

TwinsUK AF: 0.395 AC: 1466

ALSPAC AF: 0.393 AC: 1514

ESP6500AA AF: 0.456 AC: 2007

ESP6500EA AF: 0.397 AC: 3418

ExAC AF: 0.358 AC: 43474

Asia WGS AF: 0.267 AC: 929 AN: 3478

EpiCase AF: 0.397

EpiControl AF: 0.384

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	15
DANN	Benign	0.42
DEOGEN2	Benign	0.076	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.084	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-2.1	N
PhyloP100		1.3
PrimateAI	Benign	0.43	T
REVEL	Benign	0.17
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.026
ClinPred		0.0070	T
GERP RS		5.6
Varity_R		0.046
gMVP		0.43
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1718119; hg19: chr12-121615103; COSMIC: COSV55853284;