rs12815078

chr12-121184204-A-G

Variant summary

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

The NM_002562.6(P2RX7):c.1291-101A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.079 in 1,372,304 control chromosomes in the GnomAD database, including 4,679 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 0.067 (370 hom., cov: 32)
  • Exomes 𝑓: 0.081 (4309 hom.)
• Consequence: P2RX7 NM_002562.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.25

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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
P2RX7	NM_002562.6	c.1291-101A>G		intron_variant		ENST00000328963.10
LOC105370032	XR_001749352.3	n.327+19294T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
P2RX7	ENST00000328963.10	c.1291-101A>G		intron_variant		1	NM_002562.6	P1
	ENST00000652651.1	n.3548+1997T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0669 AC: 10176 AN: 152206 Hom.: 370 Cov.: 32

Gnomad AFR AF: 0.0373

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.0631

Gnomad ASJ AF: 0.0614

Gnomad EAS AF: 0.0630

Gnomad SAS AF: 0.0403

Gnomad FIN AF: 0.0618

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0872

Gnomad OTH AF: 0.0788

GnomAD4 exome AF: 0.0805 AC: 98219 AN: 1219980 Hom.: 4309 AF XY: 0.0799 AC XY: 47880 AN XY: 599084

Gnomad4 AFR exome AF: 0.0340

Gnomad4 AMR exome AF: 0.0498

Gnomad4 ASJ exome AF: 0.0675

Gnomad4 EAS exome AF: 0.0569

Gnomad4 SAS exome AF: 0.0447

Gnomad4 FIN exome AF: 0.0609

Gnomad4 NFE exome AF: 0.0869

Gnomad4 OTH exome AF: 0.0780

GnomAD4 genome AF: 0.0668 AC: 10176 AN: 152324 Hom.: 370 Cov.: 32 AF XY: 0.0644 AC XY: 4794 AN XY: 74484

Gnomad4 AFR AF: 0.0372

Gnomad4 AMR AF: 0.0628

Gnomad4 ASJ AF: 0.0614

Gnomad4 EAS AF: 0.0626

Gnomad4 SAS AF: 0.0405

Gnomad4 FIN AF: 0.0618

Gnomad4 NFE AF: 0.0872

Gnomad4 OTH AF: 0.0784

Alfa AF: 0.0768 Hom.: 235

Bravo AF: 0.0660

Asia WGS AF: 0.0590 AC: 203 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.012
Dann	Benign	0.21

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: rs12815078; hg19: chr12-121622007;