rs3751144

Positions:

• chr12-121184436-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000328963.10(P2RX7):​c.1422C>T​(p.Pro474=) 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 1,613,982 control chromosomes in the GnomAD database, including 10,364 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 (1436 hom., cov: 32)
  • Exomes 𝑓: 0.094 (8928 hom.)
• Consequence: P2RX7 ENST00000328963.10 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.23

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP7: Synonymous conserved (PhyloP=-6.23 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P2RX7	NM_002562.6	c.1422C>T	p.Pro474=	synonymous_variant	13/13	ENST00000328963.10	NP_002553.3
LOC105370032	XR_001749352.3	n.327+19062G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
P2RX7	ENST00000328963.10	c.1422C>T	p.Pro474=	synonymous_variant	13/13	1	NM_002562.6	ENSP00000330696	P1
	ENST00000652651.1	n.3548+1765G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18565 AN: 152040 Hom.: 1424 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.0308

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.0554

Gnomad EAS AF: 0.162

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

GnomAD3 exomes AF: 0.141 AC: 35400 AN: 251364 Hom.: 3886 AF XY: 0.131 AC XY: 17866 AN XY: 135872

Gnomad AFR exome AF: 0.156

Gnomad AMR exome AF: 0.359

Gnomad ASJ exome AF: 0.0587

Gnomad EAS exome AF: 0.173

Gnomad SAS exome AF: 0.155

Gnomad FIN exome AF: 0.126

Gnomad NFE exome AF: 0.0751

Gnomad OTH exome AF: 0.113

GnomAD4 exome AF: 0.0942 AC: 137726 AN: 1461824 Hom.: 8928 Cov.: 37 AF XY: 0.0939 AC XY: 68274 AN XY: 727222

Gnomad4 AFR exome AF: 0.153

Gnomad4 AMR exome AF: 0.338

Gnomad4 ASJ exome AF: 0.0601

Gnomad4 EAS exome AF: 0.156

Gnomad4 SAS exome AF: 0.150

Gnomad4 FIN exome AF: 0.127

Gnomad4 NFE exome AF: 0.0752

Gnomad4 OTH exome AF: 0.100

GnomAD4 genome AF: 0.122 AC: 18609 AN: 152158 Hom.: 1436 Cov.: 32 AF XY: 0.126 AC XY: 9374 AN XY: 74372

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.0554

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.0777

Gnomad4 OTH AF: 0.106

Alfa AF: 0.0883 Hom.: 1408

Bravo AF: 0.131

Asia WGS AF: 0.180 AC: 627 AN: 3478

EpiCase AF: 0.0671

EpiControl AF: 0.0708

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.058
DANN	Benign	0.84

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

Publications

LitVar

Other links and lift over

dbSNP: rs3751144; hg19: chr12-121622239; COSMIC: COSV55853264;