12-121156253-G-A

Variant names:

• chr12-121156253-G-A
• rs208290
• NM_002562.6:c.363+106G>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.363+106G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 867,118 control chromosomes in the GnomAD database, including 54,764 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 0.42 (16894 hom., cov: 31)
  • Exomes 𝑓: 0.31 (37870 hom.)
• Consequence: P2RX7 NM_002562.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.464
• Publications: 7 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.748 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.363+106G>A		intron	N/A	NP_002553.3
	P2RX7	NR_033948.2		n.597+106G>A		intron	N/A
	P2RX7	NR_033949.2		n.597+106G>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.363+106G>A		intron	N/A	ENSP00000330696.6
	P2RX7	ENST00000261826.10	TSL:1	n.363+106G>A		intron	N/A	ENSP00000261826.6
	P2RX7	ENST00000538011.5	TSL:1	n.*118+106G>A		intron	N/A	ENSP00000439247.1

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63802 AN: 151910 Hom.: 16833 Cov.: 31

Gnomad AFR AF: 0.755

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.343

GnomAD4 exome AF: 0.311 AC: 222228 AN: 715090 Hom.: 37870 AF XY: 0.312 AC XY: 118396 AN XY: 379786

African (AFR) AF: 0.760 AC: 14252 AN: 18754

American (AMR) AF: 0.177 AC: 6454 AN: 36386

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 4195 AN: 19568

East Asian (EAS) AF: 0.380 AC: 13565 AN: 35736

South Asian (SAS) AF: 0.386 AC: 25789 AN: 66806

European-Finnish (FIN) AF: 0.393 AC: 20036 AN: 50922

Middle Eastern (MID) AF: 0.234 AC: 620 AN: 2646

European-Non Finnish (NFE) AF: 0.281 AC: 126161 AN: 449178

Other (OTH) AF: 0.318 AC: 11156 AN: 35094

GnomAD4 genome AF: 0.421 AC: 63940 AN: 152028 Hom.: 16894 Cov.: 31 AF XY: 0.418 AC XY: 31080 AN XY: 74308

African (AFR) AF: 0.755 AC: 31306 AN: 41458

American (AMR) AF: 0.249 AC: 3804 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 745 AN: 3470

East Asian (EAS) AF: 0.377 AC: 1944 AN: 5154

South Asian (SAS) AF: 0.393 AC: 1892 AN: 4816

European-Finnish (FIN) AF: 0.388 AC: 4100 AN: 10560

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.282 AC: 19173 AN: 67970

Other (OTH) AF: 0.344 AC: 726 AN: 2108

Alfa AF: 0.340 Hom.: 4231

Bravo AF: 0.420

Asia WGS AF: 0.412 AC: 1434 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	0.40
DANN	Benign	0.56
PhyloP100		-0.46
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: rs208290; hg19: chr12-121594056; COSMIC: COSV55854655;