12-121177131-C-T

Variant names:

• chr12-121177131-C-T
• rs7132846
• NM_002562.6:c.973-16C>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.973-16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0935 in 1,611,042 control chromosomes in the GnomAD database, including 9,711 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 0.11 (1107 hom., cov: 32)
  • Exomes 𝑓: 0.092 (8604 hom.)
• Consequence: P2RX7 NM_002562.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.125
• Publications: 14 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=-0.69).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RX7	NM_002562.6	c.973-16C>T		intron_variant	Intron 9 of 12	ENST00000328963.10	NP_002553.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P2RX7	ENST00000328963.10	c.973-16C>T		intron_variant	Intron 9 of 12	1	NM_002562.6	ENSP00000330696.6

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16137 AN: 152112 Hom.: 1096 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.0568

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0772

Gnomad OTH AF: 0.0890

GnomAD2 exomes AF: 0.137 AC: 34380 AN: 251032 AF XY: 0.129

Gnomad AFR exome AF: 0.0993

Gnomad AMR exome AF: 0.356

Gnomad ASJ exome AF: 0.0589

Gnomad EAS exome AF: 0.175

Gnomad FIN exome AF: 0.125

Gnomad NFE exome AF: 0.0747

Gnomad OTH exome AF: 0.111

GnomAD4 exome AF: 0.0922 AC: 134517 AN: 1458812 Hom.: 8604 Cov.: 30 AF XY: 0.0923 AC XY: 66988 AN XY: 725956

African (AFR) AF: 0.0966 AC: 3229 AN: 33436

American (AMR) AF: 0.335 AC: 14969 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.0604 AC: 1577 AN: 26122

East Asian (EAS) AF: 0.157 AC: 6213 AN: 39674

South Asian (SAS) AF: 0.151 AC: 13054 AN: 86174

European-Finnish (FIN) AF: 0.127 AC: 6771 AN: 53410

Middle Eastern (MID) AF: 0.0615 AC: 350 AN: 5688

European-Non Finnish (NFE) AF: 0.0744 AC: 82562 AN: 1109364

Other (OTH) AF: 0.0961 AC: 5792 AN: 60264

GnomAD4 genome AF: 0.106 AC: 16174 AN: 152230 Hom.: 1107 Cov.: 32 AF XY: 0.111 AC XY: 8257 AN XY: 74420

African (AFR) AF: 0.101 AC: 4214 AN: 41530

American (AMR) AF: 0.213 AC: 3259 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0568 AC: 197 AN: 3470

East Asian (EAS) AF: 0.165 AC: 855 AN: 5184

South Asian (SAS) AF: 0.164 AC: 791 AN: 4826

European-Finnish (FIN) AF: 0.128 AC: 1356 AN: 10596

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0773 AC: 5255 AN: 68020

Other (OTH) AF: 0.0942 AC: 199 AN: 2112

Alfa AF: 0.0894 Hom.: 1151

Bravo AF: 0.113

Asia WGS AF: 0.177 AC: 614 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	10
DANN	Benign	0.73
PhyloP100		-0.13
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: rs7132846; hg19: chr12-121614934;