12-121158841-A-G

Position:

• chr12-121158841-A-G

Variant summary

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

The NM_002562.6(P2RX7):​c.364-2061A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0885 in 152,252 control chromosomes in the GnomAD database, including 939 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 0.089 (939 hom., cov: 32)
• Consequence: P2RX7 NM_002562.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.891

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=-0.53).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
P2RX7	NM_002562.6	c.364-2061A>G		intron_variant		ENST00000328963.10
LOC105370032	XR_001749352.3	n.328-32000T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
P2RX7	ENST00000328963.10	c.364-2061A>G		intron_variant		1	NM_002562.6	P1

Frequencies

GnomAD3 genomes AF: 0.0884 AC: 13443 AN: 152134 Hom.: 929 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.0286

Gnomad AMR AF: 0.0421

Gnomad ASJ AF: 0.0323

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.0909

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0431

Gnomad OTH AF: 0.0588

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

GnomAD4 genome AF: 0.0885 AC: 13480 AN: 152252 Hom.: 939 Cov.: 32 AF XY: 0.0908 AC XY: 6760 AN XY: 74430

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.0429

Gnomad4 ASJ AF: 0.0323

Gnomad4 EAS AF: 0.256

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.0909

Gnomad4 NFE AF: 0.0431

Gnomad4 OTH AF: 0.0639

Alfa AF: 0.0536 Hom.: 230

Bravo AF: 0.0868

Asia WGS AF: 0.186 AC: 645 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	9.8
DANN	Benign	0.93

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: rs10849851; hg19: chr12-121596644;