chr12-121160849-G-A

Variant names:

• chr12-121160849-G-A
• rs1653583
• NM_002562.6:c.364-53G>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.364-53G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0824 in 1,325,298 control chromosomes in the GnomAD database, including 5,203 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 0.10 (965 hom., cov: 32)
  • Exomes 𝑓: 0.080 (4238 hom.)
• Consequence: P2RX7 NM_002562.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.776
• Publications: 9 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.174 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.364-53G>A		intron	N/A	NP_002553.3
	P2RX7	NR_033948.2		n.598-53G>A		intron	N/A
	P2RX7	NR_033949.2		n.598-53G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RX7	ENST00000328963.10	TSL:1 MANE Select	c.364-53G>A		intron	N/A	ENSP00000330696.6	Q99572-1
	P2RX7	ENST00000261826.10	TSL:1	n.364-53G>A		intron	N/A	ENSP00000261826.6	J3KN30
	P2RX7	ENST00000538011.5	TSL:1	n.*119-53G>A		intron	N/A	ENSP00000439247.1	F5H2X6

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15509 AN: 152048 Hom.: 964 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.0536

Gnomad ASJ AF: 0.0409

Gnomad EAS AF: 0.0664

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0668

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0786

Gnomad OTH AF: 0.0927

GnomAD4 exome AF: 0.0799 AC: 93709 AN: 1173132 Hom.: 4238 AF XY: 0.0807 AC XY: 48277 AN XY: 597970

African (AFR) AF: 0.182 AC: 5060 AN: 27744

American (AMR) AF: 0.0378 AC: 1677 AN: 44352

Ashkenazi Jewish (ASJ) AF: 0.0425 AC: 1033 AN: 24302

East Asian (EAS) AF: 0.0624 AC: 2401 AN: 38452

South Asian (SAS) AF: 0.114 AC: 9198 AN: 80508

European-Finnish (FIN) AF: 0.0694 AC: 3701 AN: 53304

Middle Eastern (MID) AF: 0.0738 AC: 387 AN: 5246

European-Non Finnish (NFE) AF: 0.0779 AC: 66065 AN: 848386

Other (OTH) AF: 0.0824 AC: 4187 AN: 50838

GnomAD4 genome AF: 0.102 AC: 15523 AN: 152166 Hom.: 965 Cov.: 32 AF XY: 0.0992 AC XY: 7380 AN XY: 74412

African (AFR) AF: 0.177 AC: 7338 AN: 41480

American (AMR) AF: 0.0535 AC: 818 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0409 AC: 142 AN: 3468

East Asian (EAS) AF: 0.0659 AC: 342 AN: 5186

South Asian (SAS) AF: 0.113 AC: 544 AN: 4824

European-Finnish (FIN) AF: 0.0668 AC: 707 AN: 10590

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0786 AC: 5345 AN: 68010

Other (OTH) AF: 0.0918 AC: 194 AN: 2114

Alfa AF: 0.0751 Hom.: 296

Bravo AF: 0.103

Asia WGS AF: 0.0890 AC: 309 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.27
DANN	Benign	0.83
PhyloP100		-0.78
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: rs1653583; hg19: chr12-121598652; COSMIC: COSV55855264;