rs7958311

Variant names:

• chr12-121167552-G-A
• rs7958311
• NM_002562.6:c.809G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-121167552-G-A
• chr12-121167552-G-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.809G>A​(p.Arg270His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 1,612,774 control chromosomes in the GnomAD database, including 51,345 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R270L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.26 (5164 hom., cov: 31)
  • Exomes 𝑓: 0.25 (46181 hom.)
• Consequence: P2RX7 NM_002562.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.413
• Publications: 106 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=7.839799E-4).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.407 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.809G>A	p.Arg270His	missense	Exon 8 of 13	NP_002553.3
	P2RX7	NR_033948.2		n.1043G>A		non_coding_transcript_exon	Exon 9 of 13
	P2RX7	NR_033949.2		n.1043G>A		non_coding_transcript_exon	Exon 9 of 14

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RX7	ENST00000328963.10	TSL:1 MANE Select	c.809G>A	p.Arg270His	missense	Exon 8 of 13	ENSP00000330696.6	Q99572-1
	P2RX7	ENST00000261826.10	TSL:1	n.*262G>A		non_coding_transcript_exon	Exon 7 of 12	ENSP00000261826.6	J3KN30
	P2RX7	ENST00000538011.5	TSL:1	n.*564G>A		non_coding_transcript_exon	Exon 9 of 14	ENSP00000439247.1	F5H2X6

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39039 AN: 151776 Hom.: 5164 Cov.: 31

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.268

GnomAD2 exomes AF: 0.247 AC: 61873 AN: 250430 AF XY: 0.240

Gnomad AFR exome AF: 0.246

Gnomad AMR exome AF: 0.250

Gnomad ASJ exome AF: 0.286

Gnomad EAS exome AF: 0.441

Gnomad FIN exome AF: 0.222

Gnomad NFE exome AF: 0.253

Gnomad OTH exome AF: 0.256

GnomAD4 exome AF: 0.247 AC: 360703 AN: 1460880 Hom.: 46181 Cov.: 33 AF XY: 0.243 AC XY: 176741 AN XY: 726790

African (AFR) AF: 0.238 AC: 7943 AN: 33432

American (AMR) AF: 0.258 AC: 11495 AN: 44622

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 7576 AN: 26098

East Asian (EAS) AF: 0.390 AC: 15459 AN: 39592

South Asian (SAS) AF: 0.110 AC: 9474 AN: 86194

European-Finnish (FIN) AF: 0.221 AC: 11809 AN: 53400

Middle Eastern (MID) AF: 0.235 AC: 1353 AN: 5760

European-Non Finnish (NFE) AF: 0.252 AC: 280200 AN: 1111440

Other (OTH) AF: 0.255 AC: 15394 AN: 60342

GnomAD4 genome AF: 0.257 AC: 39047 AN: 151894 Hom.: 5164 Cov.: 31 AF XY: 0.257 AC XY: 19048 AN XY: 74238

African (AFR) AF: 0.246 AC: 10198 AN: 41392

American (AMR) AF: 0.298 AC: 4543 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1041 AN: 3470

East Asian (EAS) AF: 0.421 AC: 2169 AN: 5148

South Asian (SAS) AF: 0.118 AC: 569 AN: 4822

European-Finnish (FIN) AF: 0.226 AC: 2389 AN: 10550

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.253 AC: 17202 AN: 67946

Other (OTH) AF: 0.265 AC: 560 AN: 2112

Alfa AF: 0.256 Hom.: 17049

Bravo AF: 0.269

TwinsUK AF: 0.247 AC: 915

ALSPAC AF: 0.255 AC: 984

ESP6500AA AF: 0.239 AC: 1054

ESP6500EA AF: 0.247 AC: 2128

ExAC AF: 0.244 AC: 29607

Asia WGS AF: 0.240 AC: 833 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Benign	0.095	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.15	T
MetaRNN	Benign	0.00078	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.41
PrimateAI	Benign	0.26	T
REVEL	Benign	0.064
Sift4G	Benign	0.13	T
Polyphen		0.98	D
Vest4		0.060
ClinPred		0.019	T
GERP RS		0.97
Varity_R		0.073
gMVP		0.48
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: rs7958311; hg19: chr12-121605355; COSMIC: COSV55853753; COSMIC: COSV55853753;