rs1653598

Positions:

• chr12-121177480-T-C

Variant summary

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

The NM_002562.6(P2RX7):​c.1188+34T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 1,601,268 control chromosomes in the GnomAD database, including 122,237 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 0.39 (11875 hom., cov: 31)
  • Exomes 𝑓: 0.39 (110362 hom.)
• Consequence: P2RX7 NM_002562.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.610

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P2RX7	NM_002562.6	c.1188+34T>C		intron_variant		ENST00000328963.10	NP_002553.3
LOC105370032	XR_001749352.3	n.327+26018A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
P2RX7	ENST00000328963.10	c.1188+34T>C		intron_variant		1	NM_002562.6	ENSP00000330696	P1

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58830 AN: 151774 Hom.: 11854 Cov.: 31

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.364

GnomAD3 exomes AF: 0.349 AC: 87301 AN: 250324 Hom.: 16768 AF XY: 0.357 AC XY: 48311 AN XY: 135304

Gnomad AFR exome AF: 0.458

Gnomad AMR exome AF: 0.168

Gnomad ASJ exome AF: 0.351

Gnomad EAS exome AF: 0.111

Gnomad SAS exome AF: 0.398

Gnomad FIN exome AF: 0.452

Gnomad NFE exome AF: 0.394

Gnomad OTH exome AF: 0.352

GnomAD4 exome AF: 0.385 AC: 558517 AN: 1449376 Hom.: 110362 Cov.: 28 AF XY: 0.386 AC XY: 278559 AN XY: 721330

Gnomad4 AFR exome AF: 0.464

Gnomad4 AMR exome AF: 0.179

Gnomad4 ASJ exome AF: 0.354

Gnomad4 EAS exome AF: 0.139

Gnomad4 SAS exome AF: 0.402

Gnomad4 FIN exome AF: 0.447

Gnomad4 NFE exome AF: 0.397

Gnomad4 OTH exome AF: 0.375

GnomAD4 genome AF: 0.388 AC: 58897 AN: 151892 Hom.: 11875 Cov.: 31 AF XY: 0.383 AC XY: 28412 AN XY: 74254

Gnomad4 AFR AF: 0.446

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.126

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.448

Gnomad4 NFE AF: 0.400

Gnomad4 OTH AF: 0.359

Alfa AF: 0.394 Hom.: 2604

Bravo AF: 0.371

Asia WGS AF: 0.270 AC: 941 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.7
DANN	Benign	0.16

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: rs1653598; hg19: chr12-121615283; COSMIC: COSV55855612;