rs2567998

chr12-121180338-A-C

Variant summary

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

The NM_002562.6(P2RX7):c.1189-16A>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00366 in 1,472,950 control chromosomes in the GnomAD database, including 172 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 0.019 (101 hom., cov: 31)
  • Exomes 𝑓: 0.0019 (71 hom.)
• Consequence: P2RX7 NM_002562.6 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0760

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
P2RX7	NM_002562.6	c.1189-16A>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000328963.10
LOC105370032	XR_001749352.3	n.327+23160T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
P2RX7	ENST00000328963.10	c.1189-16A>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_002562.6	P1
	ENST00000652651.1	n.3549-2390T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0189 AC: 2876 AN: 152100 Hom.: 101 Cov.: 31

Gnomad AFR AF: 0.0653

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00872

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.0153

GnomAD3 exomes AF: 0.00541 AC: 1183 AN: 218478 Hom.: 38 AF XY: 0.00408 AC XY: 485 AN XY: 118910

Gnomad AFR exome AF: 0.0682

Gnomad AMR exome AF: 0.00400

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000846

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000123

Gnomad OTH exome AF: 0.00331

GnomAD4 exome AF: 0.00190 AC: 2511 AN: 1320734 Hom.: 71 Cov.: 18 AF XY: 0.00163 AC XY: 1080 AN XY: 662590

Gnomad4 AFR exome AF: 0.0699

Gnomad4 AMR exome AF: 0.00404

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000196

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000775

Gnomad4 OTH exome AF: 0.00431

GnomAD4 genome AF: 0.0190 AC: 2887 AN: 152216 Hom.: 101 Cov.: 31 AF XY: 0.0183 AC XY: 1363 AN XY: 74414

Gnomad4 AFR AF: 0.0654

Gnomad4 AMR AF: 0.00871

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.0151

Alfa AF: 0.00384 Hom.: 15

Bravo AF: 0.0217

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.85
Dann	Benign	0.55

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: rs2567998; hg19: chr12-121618141;