rs891781

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

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+180C>T		intron	N/A	NP_002553.3
	P2RX7	NR_033948.2		n.1608+180C>T		intron	N/A
	P2RX7	NR_033949.2		n.1524+180C>T		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+180C>T		intron	N/A	ENSP00000330696.6	Q99572-1
	P2RX7	ENST00000261826.10	TSL:1	n.*743+180C>T		intron	N/A	ENSP00000261826.6	J3KN30
	P2RX7	ENST00000538011.5	TSL:1	n.*1045+180C>T		intron	N/A	ENSP00000439247.1	F5H2X6

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

African (AFR) AF: 0.447 AC: 18497 AN: 41410

American (AMR) AF: 0.242 AC: 3688 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1191 AN: 3470

East Asian (EAS) AF: 0.127 AC: 655 AN: 5172

South Asian (SAS) AF: 0.370 AC: 1779 AN: 4810

European-Finnish (FIN) AF: 0.448 AC: 4725 AN: 10544

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.399 AC: 27135 AN: 67946

Other (OTH) AF: 0.358 AC: 755 AN: 2108

Alfa AF: 0.395 Hom.: 6964

Bravo AF: 0.371

Asia WGS AF: 0.271 AC: 942 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.42
DANN	Benign	0.57
PhyloP100		-0.92
Mutation Taster		=100/0	polymorphism (auto)

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: rs891781; hg19: chr12-121618438;