rs891781

Variant names:

• chr12-121180635-C-T
• rs891781
• NM_002562.6:c.1290+180C>T

Variant summary

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

The NM_002562.6(P2RX7):​c.1290+180C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 151,898 control chromosomes in the GnomAD database, including 11,851 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 0.39 (11851 hom., cov: 31)
• Consequence: P2RX7 NM_002562.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.922

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RX7	NM_002562.6	c.1290+180C>T		intron_variant	Intron 12 of 12	ENST00000328963.10	NP_002553.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P2RX7	ENST00000328963.10	c.1290+180C>T		intron_variant	Intron 12 of 12	1	NM_002562.6	ENSP00000330696.6

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58804 AN: 151780 Hom.: 11830 Cov.: 31

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.363

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

GnomAD4 genome AF: 0.388 AC: 58871 AN: 151898 Hom.: 11851 Cov.: 31 AF XY: 0.382 AC XY: 28381 AN XY: 74218

Gnomad4 AFR AF: 0.447

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.343

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.448

Gnomad4 NFE AF: 0.399

Gnomad4 OTH AF: 0.358

Alfa AF: 0.394 Hom.: 6266

Bravo AF: 0.371

Asia WGS AF: 0.271 AC: 942 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.42
DANN	Benign	0.57

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: rs891781; hg19: chr12-121618438;