12-121184616-G-T

Variant names:

• chr12-121184616-G-T
• rs3751142
• NM_002562.6:c.1602G>T

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.1602G>T​(p.Leu534Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0969 in 1,611,842 control chromosomes in the GnomAD database, including 10,317 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 0.12 (1446 hom., cov: 33)
  • Exomes 𝑓: 0.094 (8871 hom.)
• Consequence: P2RX7 NM_002562.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.00
• Publications: 21 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP7: Synonymous conserved (PhyloP=3 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RX7	NM_002562.6	c.1602G>T	p.Leu534Leu	synonymous_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.1602G>T	p.Leu534Leu	synonymous_variant	Exon 13 of 13	1	NM_002562.6	ENSP00000330696.6

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18641 AN: 152170 Hom.: 1434 Cov.: 33

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.0556

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0777

Gnomad OTH AF: 0.100

GnomAD2 exomes AF: 0.142 AC: 34790 AN: 244858 AF XY: 0.133

Gnomad AFR exome AF: 0.160

Gnomad AMR exome AF: 0.360

Gnomad ASJ exome AF: 0.0589

Gnomad EAS exome AF: 0.175

Gnomad FIN exome AF: 0.126

Gnomad NFE exome AF: 0.0758

Gnomad OTH exome AF: 0.114

GnomAD4 exome AF: 0.0943 AC: 137569 AN: 1459554 Hom.: 8871 Cov.: 41 AF XY: 0.0940 AC XY: 68221 AN XY: 726014

African (AFR) AF: 0.154 AC: 5141 AN: 33360

American (AMR) AF: 0.338 AC: 14969 AN: 44242

Ashkenazi Jewish (ASJ) AF: 0.0602 AC: 1570 AN: 26082

East Asian (EAS) AF: 0.156 AC: 6173 AN: 39536

South Asian (SAS) AF: 0.150 AC: 12906 AN: 85942

European-Finnish (FIN) AF: 0.127 AC: 6736 AN: 53138

Middle Eastern (MID) AF: 0.0638 AC: 368 AN: 5766

European-Non Finnish (NFE) AF: 0.0753 AC: 83658 AN: 1111182

Other (OTH) AF: 0.100 AC: 6048 AN: 60306

GnomAD4 genome AF: 0.123 AC: 18685 AN: 152288 Hom.: 1446 Cov.: 33 AF XY: 0.127 AC XY: 9428 AN XY: 74462

African (AFR) AF: 0.158 AC: 6569 AN: 41564

American (AMR) AF: 0.220 AC: 3370 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0556 AC: 193 AN: 3470

East Asian (EAS) AF: 0.164 AC: 852 AN: 5188

South Asian (SAS) AF: 0.162 AC: 783 AN: 4826

European-Finnish (FIN) AF: 0.128 AC: 1357 AN: 10612

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0777 AC: 5287 AN: 68022

Other (OTH) AF: 0.106 AC: 223 AN: 2112

Alfa AF: 0.0932 Hom.: 372

Bravo AF: 0.132

Asia WGS AF: 0.181 AC: 630 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	2.1
DANN	Benign	0.77
PhyloP100		3.0
Mutation Taster		=100/0	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: rs3751142; hg19: chr12-121622419; COSMIC: COSV55853273;