rs1718125

chr12-121155216-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002562.6(P2RX7):c.294+263C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,426,432 control chromosomes in the GnomAD database, including 16,847 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 0.19 (3457 hom., cov: 32)
  • Exomes 𝑓: 0.13 (13390 hom.)
• Consequence: P2RX7 NM_002562.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.389

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 (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
P2RX7	NM_002562.6	c.294+263C>T		intron_variant		ENST00000328963.10
LOC105370032	XR_001749352.3	n.328-28375G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
P2RX7	ENST00000328963.10	c.294+263C>T		intron_variant		1	NM_002562.6	P1

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28714 AN: 151924 Hom.: 3449 Cov.: 32

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.0949

Gnomad ASJ AF: 0.0732

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.150

GnomAD3 exomes AF: 0.152 AC: 20159 AN: 132418 Hom.: 2013 AF XY: 0.157 AC XY: 11340 AN XY: 72260

Gnomad AFR exome AF: 0.348

Gnomad AMR exome AF: 0.0762

Gnomad ASJ exome AF: 0.0751

Gnomad EAS exome AF: 0.322

Gnomad SAS exome AF: 0.214

Gnomad FIN exome AF: 0.154

Gnomad NFE exome AF: 0.117

Gnomad OTH exome AF: 0.123

GnomAD4 exome AF: 0.135 AC: 171535 AN: 1274390 Hom.: 13390 Cov.: 32 AF XY: 0.136 AC XY: 85463 AN XY: 627134

Gnomad4 AFR exome AF: 0.351

Gnomad4 AMR exome AF: 0.0757

Gnomad4 ASJ exome AF: 0.0753

Gnomad4 EAS exome AF: 0.306

Gnomad4 SAS exome AF: 0.217

Gnomad4 FIN exome AF: 0.156

Gnomad4 NFE exome AF: 0.120

Gnomad4 OTH exome AF: 0.151

GnomAD4 genome AF: 0.189 AC: 28764 AN: 152042 Hom.: 3457 Cov.: 32 AF XY: 0.189 AC XY: 14032 AN XY: 74332

Gnomad4 AFR AF: 0.335

Gnomad4 AMR AF: 0.0955

Gnomad4 ASJ AF: 0.0732

Gnomad4 EAS AF: 0.318

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.158

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.154

Alfa AF: 0.126 Hom.: 2183

Bravo AF: 0.188

Asia WGS AF: 0.273 AC: 946 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	11
Dann	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1718125; hg19: chr12-121593019;