12-121182384-G-T

Variant names:

• chr12-121182384-G-T
• rs7312642
• NM_002562.6:c.1291-1921G>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.1291-1921G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,120 control chromosomes in the GnomAD database, including 1,449 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 0.12 (1449 hom., cov: 32)
• Consequence: P2RX7 NM_002562.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.311
• Publications: 6 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.214 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.1291-1921G>T		intron	N/A	NP_002553.3
	P2RX7	NR_033948.2		n.1609-1921G>T		intron	N/A
	P2RX7	NR_033949.2		n.1525-1921G>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RX7	ENST00000328963.10	TSL:1 MANE Select	c.1291-1921G>T		intron	N/A	ENSP00000330696.6
	P2RX7	ENST00000261826.10	TSL:1	n.*744-1921G>T		intron	N/A	ENSP00000261826.6
	P2RX7	ENST00000538011.5	TSL:1	n.*1046-1921G>T		intron	N/A	ENSP00000439247.1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18611 AN: 152002 Hom.: 1437 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.0559

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0776

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.123 AC: 18655 AN: 152120 Hom.: 1449 Cov.: 32 AF XY: 0.127 AC XY: 9409 AN XY: 74370

African (AFR) AF: 0.158 AC: 6556 AN: 41498

American (AMR) AF: 0.220 AC: 3358 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.0559 AC: 194 AN: 3470

East Asian (EAS) AF: 0.164 AC: 852 AN: 5182

South Asian (SAS) AF: 0.163 AC: 788 AN: 4824

European-Finnish (FIN) AF: 0.128 AC: 1354 AN: 10572

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

European-Non Finnish (NFE) AF: 0.0776 AC: 5277 AN: 68008

Other (OTH) AF: 0.107 AC: 225 AN: 2112

Alfa AF: 0.0850 Hom.: 456

Bravo AF: 0.132

Asia WGS AF: 0.181 AC: 630 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.2
DANN	Benign	0.50
PhyloP100		-0.31
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: rs7312642; hg19: chr12-121620187;