12-121162726-C-A

Position:

• chr12-121162726-C-A

Variant summary

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

The NM_002562.6(P2RX7):​c.533+206C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 151,932 control chromosomes in the GnomAD database, including 11,032 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 0.36 (11032 hom., cov: 30)
• Consequence: P2RX7 NM_002562.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.122

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P2RX7	NM_002562.6	c.533+206C>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.533+206C>A		intron_variant		1	NM_002562.6	ENSP00000330696.6

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54318 AN: 151814 Hom.: 10988 Cov.: 30

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.291

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.358 AC: 54435 AN: 151932 Hom.: 11032 Cov.: 30 AF XY: 0.356 AC XY: 26436 AN XY: 74282

Gnomad4 AFR AF: 0.554

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.353

Gnomad4 SAS AF: 0.331

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.273

Gnomad4 OTH AF: 0.294

Alfa AF: 0.265 Hom.: 7351

Bravo AF: 0.362

Asia WGS AF: 0.358 AC: 1246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.54
DANN	Benign	0.41

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: rs1186055; hg19: chr12-121600529;