chr12-121182384-G-T

Position:

• chr12-121182384-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000328963.10(P2RX7):​c.1291-1921G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,120 control chromosomes in the GnomAD database, including 1,449 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 0.12 (1449 hom., cov: 32)
• Consequence: P2RX7 ENST00000328963.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.311

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P2RX7	NM_002562.6	c.1291-1921G>T		intron_variant		ENST00000328963.10	NP_002553.3
LOC105370032	XR_001749352.3	n.327+21114C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
P2RX7	ENST00000328963.10	c.1291-1921G>T		intron_variant		1	NM_002562.6	ENSP00000330696	P1
	ENST00000652651.1	n.3548+3817C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18611 AN: 152002 Hom.: 1437 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.0559

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0776

Gnomad OTH AF: 0.101

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.123 AC: 18655 AN: 152120 Hom.: 1449 Cov.: 32 AF XY: 0.127 AC XY: 9409 AN XY: 74370

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.0559

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.0776

Gnomad4 OTH AF: 0.107

Alfa AF: 0.0849 Hom.: 416

Bravo AF: 0.132

Asia WGS AF: 0.181 AC: 630 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.2
DANN	Benign	0.50

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: rs7312642; hg19: chr12-121620187;