rs28360448

Positions:

• chr12-121162449-G-A

Variant summary

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

The NM_002562.6(P2RX7):​c.462G>A​(p.Val154Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0138 in 1,613,892 control chromosomes in the GnomAD database, including 744 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 0.038 (290 hom., cov: 32)
  • Exomes 𝑓: 0.011 (454 hom.)
• Consequence: P2RX7 NM_002562.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.43

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP7: Synonymous conserved (PhyloP=-2.43 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P2RX7	NM_002562.6	c.462G>A	p.Val154Val	synonymous_variant	5/13	ENST00000328963.10	NP_002553.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
P2RX7	ENST00000328963.10	c.462G>A	p.Val154Val	synonymous_variant	5/13	1	NM_002562.6	ENSP00000330696.6

Frequencies

GnomAD3 genomes AF: 0.0383 AC: 5819 AN: 152110 Hom.: 291 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0141

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0472

Gnomad FIN AF: 0.0107

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00556

Gnomad OTH AF: 0.0330

GnomAD3 exomes AF: 0.0185 AC: 4645 AN: 251112 Hom.: 178 AF XY: 0.0183 AC XY: 2480 AN XY: 135730

Gnomad AFR exome AF: 0.120

Gnomad AMR exome AF: 0.00900

Gnomad ASJ exome AF: 0.00645

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0455

Gnomad FIN exome AF: 0.00865

Gnomad NFE exome AF: 0.00570

Gnomad OTH exome AF: 0.0148

GnomAD4 exome AF: 0.0112 AC: 16374 AN: 1461662 Hom.: 454 Cov.: 33 AF XY: 0.0120 AC XY: 8710 AN XY: 727122

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.00961

Gnomad4 ASJ exome AF: 0.00624

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.0441

Gnomad4 FIN exome AF: 0.00777

Gnomad4 NFE exome AF: 0.00566

Gnomad4 OTH exome AF: 0.0159

GnomAD4 genome AF: 0.0382 AC: 5821 AN: 152230 Hom.: 290 Cov.: 32 AF XY: 0.0375 AC XY: 2789 AN XY: 74438

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.0141

Gnomad4 ASJ AF: 0.00432

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0466

Gnomad4 FIN AF: 0.0107

Gnomad4 NFE AF: 0.00556

Gnomad4 OTH AF: 0.0326

Alfa AF: 0.0253 Hom.: 87

Bravo AF: 0.0417

Asia WGS AF: 0.0270 AC: 93 AN: 3478

EpiCase AF: 0.00627

EpiControl AF: 0.00622

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.22
DANN	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs28360448; hg19: chr12-121600252;