chr12-121184393-A-G

Variant names:

• chr12-121184393-A-G
• rs2230912
• NM_002562.6:c.1379A>G

Variant summary

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

The NM_002562.6(P2RX7):​c.1379A>G​(p.Gln460Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,613,940 control chromosomes in the GnomAD database, including 20,186 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.

• Frequency:
  • Genomes: 𝑓 0.12 (1306 hom., cov: 32)
  • Exomes 𝑓: 0.16 (18880 hom.)
• Consequence: P2RX7 NM_002562.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.30
• Publications: 148 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]

ENSG00000286248 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016370714).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RX7	NM_002562.6	c.1379A>G	p.Gln460Arg	missense_variant	Exon 13 of 13	ENST00000328963.10	NP_002553.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P2RX7	ENST00000328963.10	c.1379A>G	p.Gln460Arg	missense_variant	Exon 13 of 13	1	NM_002562.6	ENSP00000330696.6

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17985 AN: 152014 Hom.: 1308 Cov.: 32

Gnomad AFR AF: 0.0492

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.0799

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.114

GnomAD2 exomes AF: 0.130 AC: 32655 AN: 251306 AF XY: 0.138

Gnomad AFR exome AF: 0.0514

Gnomad AMR exome AF: 0.0581

Gnomad ASJ exome AF: 0.167

Gnomad EAS exome AF: 0.000435

Gnomad FIN exome AF: 0.163

Gnomad NFE exome AF: 0.166

Gnomad OTH exome AF: 0.130

GnomAD4 exome AF: 0.156 AC: 227374 AN: 1461808 Hom.: 18880 Cov.: 34 AF XY: 0.156 AC XY: 113436 AN XY: 727206

African (AFR) AF: 0.0501 AC: 1678 AN: 33480

American (AMR) AF: 0.0608 AC: 2721 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 4434 AN: 26136

East Asian (EAS) AF: 0.000453 AC: 18 AN: 39700

South Asian (SAS) AF: 0.163 AC: 14076 AN: 86254

European-Finnish (FIN) AF: 0.157 AC: 8367 AN: 53378

Middle Eastern (MID) AF: 0.136 AC: 785 AN: 5766

European-Non Finnish (NFE) AF: 0.168 AC: 186591 AN: 1111974

Other (OTH) AF: 0.144 AC: 8704 AN: 60396

GnomAD4 genome AF: 0.118 AC: 17987 AN: 152132 Hom.: 1306 Cov.: 32 AF XY: 0.116 AC XY: 8659 AN XY: 74354

African (AFR) AF: 0.0493 AC: 2046 AN: 41520

American (AMR) AF: 0.0798 AC: 1219 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 572 AN: 3468

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5178

South Asian (SAS) AF: 0.141 AC: 677 AN: 4810

European-Finnish (FIN) AF: 0.162 AC: 1718 AN: 10582

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11374 AN: 67976

Other (OTH) AF: 0.112 AC: 237 AN: 2110

Alfa AF: 0.150 Hom.: 6843

Bravo AF: 0.108

TwinsUK AF: 0.167 AC: 621

ALSPAC AF: 0.164 AC: 633

ESP6500AA AF: 0.0527 AC: 232

ESP6500EA AF: 0.166 AC: 1429

ExAC AF: 0.132 AC: 15978

Asia WGS AF: 0.0640 AC: 224 AN: 3478

EpiCase AF: 0.169

EpiControl AF: 0.164

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.090
CADD	Benign	16
DANN	Benign	0.87
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.56	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		2.3
PrimateAI	Benign	0.32	T
REVEL	Benign	0.22
Sift4G	Benign	0.41	T
Vest4		0.021
ClinPred		0.011	T
GERP RS		5.2
Varity_R		0.065
gMVP		0.24
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2230912; hg19: chr12-121622196; COSMIC: COSV55854311;