12-121162377-C-T

Position:

• chr12-121162377-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.437-47C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 1,607,898 control chromosomes in the GnomAD database, including 88,479 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 (16320 hom., cov: 31)
  • Exomes 𝑓: 0.30 (72159 hom.)
• Consequence: P2RX7 NM_002562.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.797

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]

P2RX7 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 = 0.727 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P2RX7	NM_002562.6	c.437-47C>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.437-47C>T		intron_variant		1	NM_002562.6	ENSP00000330696.6

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63124 AN: 151876 Hom.: 16258 Cov.: 31

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.340

GnomAD3 exomes AF: 0.324 AC: 78843 AN: 243444 Hom.: 14988 AF XY: 0.322 AC XY: 42246 AN XY: 131390

Gnomad AFR exome AF: 0.748

Gnomad AMR exome AF: 0.162

Gnomad ASJ exome AF: 0.209

Gnomad EAS exome AF: 0.390

Gnomad SAS exome AF: 0.406

Gnomad FIN exome AF: 0.406

Gnomad NFE exome AF: 0.276

Gnomad OTH exome AF: 0.288

GnomAD4 exome AF: 0.302 AC: 439160 AN: 1455904 Hom.: 72159 Cov.: 32 AF XY: 0.303 AC XY: 219600 AN XY: 723846

Gnomad4 AFR exome AF: 0.753

Gnomad4 AMR exome AF: 0.172

Gnomad4 ASJ exome AF: 0.211

Gnomad4 EAS exome AF: 0.413

Gnomad4 SAS exome AF: 0.404

Gnomad4 FIN exome AF: 0.401

Gnomad4 NFE exome AF: 0.278

Gnomad4 OTH exome AF: 0.317

GnomAD4 genome AF: 0.416 AC: 63262 AN: 151994 Hom.: 16320 Cov.: 31 AF XY: 0.415 AC XY: 30826 AN XY: 74288

Gnomad4 AFR AF: 0.734

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.399

Gnomad4 SAS AF: 0.416

Gnomad4 FIN AF: 0.395

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.342

Alfa AF: 0.324 Hom.: 5238

Bravo AF: 0.414

Asia WGS AF: 0.429 AC: 1493 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.1
DANN	Benign	0.75

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: rs208293; hg19: chr12-121600180;