rs208290

Positions:

• chr12-121156253-G-A

Variant summary

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

The NM_002562.6(P2RX7):​c.363+106G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 867,118 control chromosomes in the GnomAD database, including 54,764 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 0.42 (16894 hom., cov: 31)
  • Exomes 𝑓: 0.31 (37870 hom.)
• Consequence: P2RX7 NM_002562.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.464

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P2RX7	NM_002562.6	c.363+106G>A		intron_variant		ENST00000328963.10	NP_002553.3
LOC105370032	XR_001749352.3	n.328-29412C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
P2RX7	ENST00000328963.10	c.363+106G>A		intron_variant		1	NM_002562.6	ENSP00000330696	P1

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63802 AN: 151910 Hom.: 16833 Cov.: 31

Gnomad AFR AF: 0.755

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.343

GnomAD4 exome AF: 0.311 AC: 222228 AN: 715090 Hom.: 37870 AF XY: 0.312 AC XY: 118396 AN XY: 379786

Gnomad4 AFR exome AF: 0.760

Gnomad4 AMR exome AF: 0.177

Gnomad4 ASJ exome AF: 0.214

Gnomad4 EAS exome AF: 0.380

Gnomad4 SAS exome AF: 0.386

Gnomad4 FIN exome AF: 0.393

Gnomad4 NFE exome AF: 0.281

Gnomad4 OTH exome AF: 0.318

GnomAD4 genome AF: 0.421 AC: 63940 AN: 152028 Hom.: 16894 Cov.: 31 AF XY: 0.418 AC XY: 31080 AN XY: 74308

Gnomad4 AFR AF: 0.755

Gnomad4 AMR AF: 0.249

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.377

Gnomad4 SAS AF: 0.393

Gnomad4 FIN AF: 0.388

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.344

Alfa AF: 0.338 Hom.: 3438

Bravo AF: 0.420

Asia WGS AF: 0.412 AC: 1434 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.40
DANN	Benign	0.56

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: rs208290; hg19: chr12-121594056; COSMIC: COSV55854655;