rs654856

Positions:

• chr12-121165319-C-A
• chr12-121165319-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.534-38C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,556,476 control chromosomes in the GnomAD database, including 74,697 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 0.30 (6929 hom., cov: 31)
  • Exomes 𝑓: 0.31 (67768 hom.)
• Consequence: P2RX7 NM_002562.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.203

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]

P2RX7 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P2RX7	NM_002562.6	c.534-38C>A		intron_variant		ENST00000328963.10	NP_002553.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
P2RX7	ENST00000328963.10	c.534-38C>A		intron_variant		1	NM_002562.6	ENSP00000330696.6

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45207 AN: 151772 Hom.: 6918 Cov.: 31

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.282

GnomAD3 exomes AF: 0.271 AC: 67837 AN: 250010 Hom.: 9926 AF XY: 0.281 AC XY: 37920 AN XY: 135120

Gnomad AFR exome AF: 0.334

Gnomad AMR exome AF: 0.139

Gnomad ASJ exome AF: 0.216

Gnomad EAS exome AF: 0.110

Gnomad SAS exome AF: 0.337

Gnomad FIN exome AF: 0.295

Gnomad NFE exome AF: 0.312

Gnomad OTH exome AF: 0.272

GnomAD4 exome AF: 0.305 AC: 429052 AN: 1404584 Hom.: 67768 Cov.: 22 AF XY: 0.307 AC XY: 215455 AN XY: 702058

Gnomad4 AFR exome AF: 0.343

Gnomad4 AMR exome AF: 0.147

Gnomad4 ASJ exome AF: 0.215

Gnomad4 EAS exome AF: 0.139

Gnomad4 SAS exome AF: 0.341

Gnomad4 FIN exome AF: 0.289

Gnomad4 NFE exome AF: 0.318

Gnomad4 OTH exome AF: 0.296

GnomAD4 genome AF: 0.298 AC: 45254 AN: 151892 Hom.: 6929 Cov.: 31 AF XY: 0.293 AC XY: 21783 AN XY: 74242

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.123

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.294

Gnomad4 NFE AF: 0.314

Gnomad4 OTH AF: 0.278

Alfa AF: 0.299 Hom.: 1539

Bravo AF: 0.288

Asia WGS AF: 0.225 AC: 782 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.6
DANN	Benign	0.48

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: rs654856; hg19: chr12-121603122; COSMIC: COSV55857474; COSMIC: COSV55857474;