rs2857589

Variant names:

• chr12-121166673-C-A
• rs2857589
• NM_002562.6:c.744+486C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002562.6(P2RX7):​c.744+486C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0634 in 152,120 control chromosomes in the GnomAD database, including 350 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 0.063 (350 hom., cov: 30)
• Consequence: P2RX7 NM_002562.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.08
• Publications: 5 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]

ENSG00000295862 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0862 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RX7	NM_002562.6	MANE Select	c.744+486C>A		intron	N/A	NP_002553.3
	P2RX7	NR_033948.2		n.978+486C>A		intron	N/A
	P2RX7	NR_033949.2		n.978+486C>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RX7	ENST00000328963.10	TSL:1 MANE Select	c.744+486C>A		intron	N/A	ENSP00000330696.6
	P2RX7	ENST00000261826.10	TSL:1	n.*197+486C>A		intron	N/A	ENSP00000261826.6
	P2RX7	ENST00000538011.5	TSL:1	n.*499+486C>A		intron	N/A	ENSP00000439247.1

Frequencies

GnomAD3 genomes AF: 0.0634 AC: 9640 AN: 152002 Hom.: 348 Cov.: 30

Gnomad AFR AF: 0.0271

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.0762

Gnomad ASJ AF: 0.0421

Gnomad EAS AF: 0.0635

Gnomad SAS AF: 0.0928

Gnomad FIN AF: 0.0343

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0849

Gnomad OTH AF: 0.0762

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

GnomAD4 genome AF: 0.0634 AC: 9639 AN: 152120 Hom.: 350 Cov.: 30 AF XY: 0.0607 AC XY: 4514 AN XY: 74364

African (AFR) AF: 0.0270 AC: 1122 AN: 41506

American (AMR) AF: 0.0759 AC: 1159 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0421 AC: 146 AN: 3472

East Asian (EAS) AF: 0.0631 AC: 326 AN: 5170

South Asian (SAS) AF: 0.0933 AC: 449 AN: 4812

European-Finnish (FIN) AF: 0.0343 AC: 363 AN: 10588

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0849 AC: 5774 AN: 67986

Other (OTH) AF: 0.0754 AC: 159 AN: 2108

Alfa AF: 0.0772 Hom.: 757

Bravo AF: 0.0632

Asia WGS AF: 0.0740 AC: 256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.12
DANN	Benign	0.57
PhyloP100		-2.1
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: rs2857589; hg19: chr12-121604476;