rs1718119

Positions:

• chr12-121177300-G-A
• chr12-121177300-G-T

Variant summary

Our verdict is Benign. Variant got -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. 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 0.39 (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

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]

LOC105370032 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P2RX7	NM_002562.6	c.1042G>A	p.Ala348Thr	missense_variant	11/13	ENST00000328963.10	NP_002553.3
LOC105370032	XR_001749352.3	n.327+26198C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
P2RX7	ENST00000328963.10	c.1042G>A	p.Ala348Thr	missense_variant	11/13	1	NM_002562.6	ENSP00000330696	P1

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

GnomAD3 exomes AF: 0.348 AC: 87591 AN: 251412 Hom.: 16841 AF XY: 0.357 AC XY: 48458 AN XY: 135870

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 SAS exome AF: 0.396

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

Gnomad4 AFR exome AF: 0.464

Gnomad4 AMR exome AF: 0.179

Gnomad4 ASJ exome AF: 0.354

Gnomad4 EAS exome AF: 0.139

Gnomad4 SAS exome AF: 0.399

Gnomad4 FIN exome AF: 0.447

Gnomad4 NFE exome AF: 0.397

Gnomad4 OTH exome AF: 0.373

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

Gnomad4 AFR AF: 0.447

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.368

Gnomad4 FIN AF: 0.449

Gnomad4 NFE AF: 0.399

Gnomad4 OTH AF: 0.359

Alfa AF: 0.382 Hom.: 29605

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 v4.3

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
MutationTaster	Benign	1.0	P;P;P;P
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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1718119; hg19: chr12-121615103; COSMIC: COSV55853284;