12-121165319-C-A

Variant names:

• chr12-121165319-C-A
• rs654856
• NM_002562.6:c.534-38C>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.534-38C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,556,476 control chromosomes in the GnomAD database, including 74,697 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 0.30 (6929 hom., cov: 31)
  • Exomes 𝑓: 0.31 (67768 hom.)
• Consequence: P2RX7 NM_002562.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.203
• 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]

ENSG00000295862 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.325 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.534-38C>A		intron	N/A	NP_002553.3
	P2RX7	NR_033948.2		n.768-38C>A		intron	N/A
	P2RX7	NR_033949.2		n.768-38C>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.534-38C>A		intron	N/A	ENSP00000330696.6	Q99572-1
	P2RX7	ENST00000261826.10	TSL:1	n.437-38C>A		intron	N/A	ENSP00000261826.6	J3KN30
	P2RX7	ENST00000538011.5	TSL:1	n.*289-38C>A		intron	N/A	ENSP00000439247.1	F5H2X6

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45207 AN: 151772 Hom.: 6918 Cov.: 31

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.282

GnomAD2 exomes AF: 0.271 AC: 67837 AN: 250010 AF XY: 0.281

Gnomad AFR exome AF: 0.334

Gnomad AMR exome AF: 0.139

Gnomad ASJ exome AF: 0.216

Gnomad EAS exome AF: 0.110

Gnomad FIN exome AF: 0.295

Gnomad NFE exome AF: 0.312

Gnomad OTH exome AF: 0.272

GnomAD4 exome AF: 0.305 AC: 429052 AN: 1404584 Hom.: 67768 Cov.: 22 AF XY: 0.307 AC XY: 215455 AN XY: 702058

African (AFR) AF: 0.343 AC: 11113 AN: 32412

American (AMR) AF: 0.147 AC: 6570 AN: 44618

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 5529 AN: 25760

East Asian (EAS) AF: 0.139 AC: 5473 AN: 39428

South Asian (SAS) AF: 0.341 AC: 28952 AN: 85006

European-Finnish (FIN) AF: 0.289 AC: 15268 AN: 52854

Middle Eastern (MID) AF: 0.298 AC: 1688 AN: 5660

European-Non Finnish (NFE) AF: 0.318 AC: 337154 AN: 1060286

Other (OTH) AF: 0.296 AC: 17305 AN: 58560

GnomAD4 genome AF: 0.298 AC: 45254 AN: 151892 Hom.: 6929 Cov.: 31 AF XY: 0.293 AC XY: 21783 AN XY: 74242

African (AFR) AF: 0.330 AC: 13642 AN: 41390

American (AMR) AF: 0.213 AC: 3259 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 760 AN: 3464

East Asian (EAS) AF: 0.123 AC: 637 AN: 5160

South Asian (SAS) AF: 0.324 AC: 1558 AN: 4808

European-Finnish (FIN) AF: 0.294 AC: 3110 AN: 10570

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.314 AC: 21358 AN: 67920

Other (OTH) AF: 0.278 AC: 587 AN: 2108

Alfa AF: 0.306 Hom.: 10107

Bravo AF: 0.288

Asia WGS AF: 0.225 AC: 782 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.6
DANN	Benign	0.48
PhyloP100		-0.20
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: rs654856; hg19: chr12-121603122; COSMIC: COSV55857474; COSMIC: COSV55857474;