chr12-121177131-C-T

Position:

• chr12-121177131-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
P2RX7	NM_002562.6	c.973-16C>T		intron_variant		ENST00000328963.10	NP_002553.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
P2RX7	ENST00000328963.10	c.973-16C>T		intron_variant		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

GnomAD3 exomes AF: 0.137 AC: 34380 AN: 251032 Hom.: 3735 AF XY: 0.129 AC XY: 17498 AN XY: 135684

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 SAS exome AF: 0.157

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

Gnomad4 AFR exome AF: 0.0966

Gnomad4 AMR exome AF: 0.335

Gnomad4 ASJ exome AF: 0.0604

Gnomad4 EAS exome AF: 0.157

Gnomad4 SAS exome AF: 0.151

Gnomad4 FIN exome AF: 0.127

Gnomad4 NFE exome AF: 0.0744

Gnomad4 OTH exome AF: 0.0961

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

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.0568

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.0773

Gnomad4 OTH AF: 0.0942

Alfa AF: 0.0857 Hom.: 840

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs7132846; hg19: chr12-121614934;