NM_002562.6:c.125+567C>A

Variant names:

• chr12-121133662-C-A
• rs591874
• NM_002562.6:c.125+567C>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.125+567C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 152,078 control chromosomes in the GnomAD database, including 31,315 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 0.61 (31315 hom., cov: 32)
• Consequence: P2RX7 NM_002562.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.708
• Publications: 12 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]

LOC105370032 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.759 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.125+567C>A		intron	N/A	NP_002553.3
	P2RX7	NR_033948.2		n.220+567C>A		intron	N/A
	P2RX7	NR_033949.2		n.220+567C>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.125+567C>A		intron	N/A	ENSP00000330696.6
	P2RX7	ENST00000261826.10	TSL:1	n.125+567C>A		intron	N/A	ENSP00000261826.6
	P2RX7	ENST00000538011.5	TSL:1	n.125+567C>A		intron	N/A	ENSP00000439247.1

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92564 AN: 151960 Hom.: 31326 Cov.: 32

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.799

Gnomad AMR AF: 0.771

Gnomad ASJ AF: 0.795

Gnomad EAS AF: 0.617

Gnomad SAS AF: 0.608

Gnomad FIN AF: 0.651

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.743

Gnomad OTH AF: 0.673

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

GnomAD4 genome AF: 0.609 AC: 92562 AN: 152078 Hom.: 31315 Cov.: 32 AF XY: 0.611 AC XY: 45384 AN XY: 74338

African (AFR) AF: 0.293 AC: 12128 AN: 41462

American (AMR) AF: 0.771 AC: 11786 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.795 AC: 2760 AN: 3472

East Asian (EAS) AF: 0.617 AC: 3196 AN: 5178

South Asian (SAS) AF: 0.606 AC: 2923 AN: 4822

European-Finnish (FIN) AF: 0.651 AC: 6870 AN: 10550

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.743 AC: 50516 AN: 67986

Other (OTH) AF: 0.672 AC: 1419 AN: 2112

Alfa AF: 0.704 Hom.: 19857

Bravo AF: 0.609

Asia WGS AF: 0.589 AC: 2051 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.4
DANN	Benign	0.83
PhyloP100		-0.71
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: rs591874; hg19: chr12-121571465;