chr12-121164332-C-A

Variant names:

• chr12-121164332-C-A
• rs11065464
• NM_002562.6:c.534-1025C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002562.6(P2RX7):​c.534-1025C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 152,162 control chromosomes in the GnomAD database, including 3,721 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 0.20 (3721 hom., cov: 32)
• Consequence: P2RX7 NM_002562.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.185
• Publications: 10 publications found

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]

ENSG00000295862 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RX7	NM_002562.6	c.534-1025C>A		intron_variant	Intron 5 of 12	ENST00000328963.10	NP_002553.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P2RX7	ENST00000328963.10	c.534-1025C>A		intron_variant	Intron 5 of 12	1	NM_002562.6	ENSP00000330696.6

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31165 AN: 152044 Hom.: 3724 Cov.: 32

Gnomad AFR AF: 0.0962

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.0788

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.205 AC: 31155 AN: 152162 Hom.: 3721 Cov.: 32 AF XY: 0.203 AC XY: 15074 AN XY: 74390

African (AFR) AF: 0.0961 AC: 3990 AN: 41538

American (AMR) AF: 0.246 AC: 3757 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1015 AN: 3472

East Asian (EAS) AF: 0.319 AC: 1652 AN: 5174

South Asian (SAS) AF: 0.0788 AC: 380 AN: 4820

European-Finnish (FIN) AF: 0.195 AC: 2063 AN: 10570

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.258 AC: 17508 AN: 67982

Other (OTH) AF: 0.236 AC: 498 AN: 2114

Alfa AF: 0.247 Hom.: 8506

Bravo AF: 0.210

Asia WGS AF: 0.177 AC: 617 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.45
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11065464; hg19: chr12-121602135;