rs12829218

chr12-121180588-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 92 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
P2RX7	NM_002562.6	c.1290+133A>G		intron_variant		ENST00000328963.10
LOC105370032	XR_001749352.3	n.327+22910T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
P2RX7	ENST00000328963.10	c.1290+133A>G		intron_variant		1	NM_002562.6	P1
	ENST00000652651.1	n.3549-2640T>C		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR exome AF: 0.00904

Gnomad4 AMR exome AF: 0.0330

Gnomad4 ASJ exome AF: 0.0527

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00927

Gnomad4 FIN exome AF: 0.0351

Gnomad4 NFE exome AF: 0.0434

Gnomad4 OTH exome AF: 0.0368

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

Gnomad4 AFR AF: 0.00857

Gnomad4 AMR AF: 0.0365

Gnomad4 ASJ AF: 0.0487

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00828

Gnomad4 FIN AF: 0.0357

Gnomad4 NFE AF: 0.0438

Gnomad4 OTH AF: 0.0389

Alfa AF: 0.0369 Hom.: 61

Bravo AF: 0.0302

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	8.4
Dann	Benign	0.75

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: rs12829218; hg19: chr12-121618391;