rs12829218

Variant names:

• chr12-121180588-A-G
• rs12829218
• NM_002562.6:c.1290+133A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_002562.6(P2RX7):​c.1290+133A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0342 in 491,852 control chromosomes in the GnomAD database, including 380 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 0.030 (92 hom., cov: 31)
  • Exomes 𝑓: 0.036 (288 hom.)
• Consequence: P2RX7 NM_002562.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.893
• Publications: 3 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]

ENSG00000286248 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0305 (4641/152212) while in subpopulation NFE AF = 0.0438 (2982/68016). AF 95% confidence interval is 0.0425. There are 92 homozygotes in GnomAd4. There are 2207 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 92 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002562.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RX7	NM_002562.6	MANE Select	c.1290+133A>G		intron	N/A	NP_002553.3
	P2RX7	NR_033948.2		n.1608+133A>G		intron	N/A
	P2RX7	NR_033949.2		n.1524+133A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RX7	ENST00000328963.10	TSL:1 MANE Select	c.1290+133A>G		intron	N/A	ENSP00000330696.6	Q99572-1
	P2RX7	ENST00000261826.10	TSL:1	n.*743+133A>G		intron	N/A	ENSP00000261826.6	J3KN30
	P2RX7	ENST00000538011.5	TSL:1	n.*1045+133A>G		intron	N/A	ENSP00000439247.1	F5H2X6

Frequencies

GnomAD3 genomes AF: 0.0305 AC: 4641 AN: 152094 Hom.: 92 Cov.: 31

Gnomad AFR AF: 0.00859

Gnomad AMI AF: 0.0705

Gnomad AMR AF: 0.0367

Gnomad ASJ AF: 0.0487

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00807

Gnomad FIN AF: 0.0357

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0438

Gnomad OTH AF: 0.0393

GnomAD4 exome AF: 0.0358 AC: 12162 AN: 339640 Hom.: 288 AF XY: 0.0350 AC XY: 6265 AN XY: 178750

African (AFR) AF: 0.00904 AC: 81 AN: 8964

American (AMR) AF: 0.0330 AC: 369 AN: 11170

Ashkenazi Jewish (ASJ) AF: 0.0527 AC: 580 AN: 10998

East Asian (EAS) AF: 0.00 AC: 0 AN: 25816

South Asian (SAS) AF: 0.00927 AC: 204 AN: 22012

European-Finnish (FIN) AF: 0.0351 AC: 1021 AN: 29088

Middle Eastern (MID) AF: 0.0323 AC: 58 AN: 1798

European-Non Finnish (NFE) AF: 0.0434 AC: 9117 AN: 209888

Other (OTH) AF: 0.0368 AC: 732 AN: 19906

GnomAD4 genome AF: 0.0305 AC: 4641 AN: 152212 Hom.: 92 Cov.: 31 AF XY: 0.0297 AC XY: 2207 AN XY: 74410

African (AFR) AF: 0.00857 AC: 356 AN: 41546

American (AMR) AF: 0.0365 AC: 558 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0487 AC: 169 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.00828 AC: 40 AN: 4830

European-Finnish (FIN) AF: 0.0357 AC: 378 AN: 10580

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0438 AC: 2982 AN: 68016

Other (OTH) AF: 0.0389 AC: 82 AN: 2108

Alfa AF: 0.0375 Hom.: 68

Bravo AF: 0.0302

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.4
DANN	Benign	0.75
PhyloP100		0.89
Mutation Taster		=100/0	polymorphism

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: rs12829218; hg19: chr12-121618391;