12-121158841-A-G

Variant names:

• chr12-121158841-A-G
• rs10849851
• NM_002562.6:c.364-2061A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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]

LOC105370032 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
P2RX7	NM_002562.6	c.364-2061A>G		intron_variant	Intron 3 of 12	ENST00000328963.10	NP_002553.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P2RX7	ENST00000328963.10	c.364-2061A>G		intron_variant	Intron 3 of 12	1	NM_002562.6	ENSP00000330696.6

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

African (AFR) AF: 0.162 AC: 6743 AN: 41544

American (AMR) AF: 0.0429 AC: 657 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0323 AC: 112 AN: 3470

East Asian (EAS) AF: 0.256 AC: 1326 AN: 5170

South Asian (SAS) AF: 0.120 AC: 577 AN: 4824

European-Finnish (FIN) AF: 0.0909 AC: 963 AN: 10594

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0431 AC: 2934 AN: 68028

Other (OTH) AF: 0.0639 AC: 135 AN: 2114

Alfa AF: 0.0543 Hom.: 269

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
PhyloP100		0.89
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: rs10849851; hg19: chr12-121596644;