dbSNP rs12829218: P2RX7:c.1290+133A>G (chr12-121180588-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_002562.6(P2RX7):c.1290+133A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0342 in 491,852 control chromosomes in the GnomAD database, including 380 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 0.030 ( 92 hom., cov: 31)

Exomes 𝑓: 0.036 ( 288 hom. )

Consequence

P2RX7
NM_002562.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.893

Publications

3 publications found

Variant links:

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 links:

ENSG00000286248 (HGNC:):

ENSG00000286248 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0305 (4641/152212) while in subpopulation NFE AF = 0.0438 (2982/68016). AF 95% confidence interval is 0.0425. There are 92 homozygotes in GnomAd4. There are 2207 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 92 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RX7	NM_002562.6 link	c.1290+133A>G		intron_variant	Intron 12 of 12	ENST00000328963.10	NP_002553.3	Q99572-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P2RX7	ENST00000328963.10 link	c.1290+133A>G		intron_variant	Intron 12 of 12	1	NM_002562.6	ENSP00000330696.6		Q99572-1

Frequencies

GnomAD3 genomes

AF:

0.0305

AC:

4641

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00859

Gnomad AMI

AF:

0.0705

Gnomad AMR

AF:

0.0367

Gnomad ASJ

AF:

0.0487

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00807

Gnomad FIN

AF:

0.0357

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0438

Gnomad OTH

AF:

0.0393

GnomAD4 exome

AF:

0.0358

AC:

12162

AN:

339640

Hom.:

288

AF XY:

0.0350

AC XY:

6265

AN XY:

178750

show subpopulations

African (AFR)

AF:

0.00904

AC:

AN:

8964

American (AMR)

AF:

0.0330

AC:

369

AN:

11170

Ashkenazi Jewish (ASJ)

AF:

0.0527

AC:

580

AN:

10998

East Asian (EAS)

AF:

0.00

AC:

AN:

25816

South Asian (SAS)

AF:

0.00927

AC:

204

AN:

22012

European-Finnish (FIN)

AF:

0.0351

AC:

1021

AN:

29088

Middle Eastern (MID)

AF:

0.0323

AC:

AN:

1798

European-Non Finnish (NFE)

AF:

0.0434

AC:

9117

AN:

209888

Other (OTH)

AF:

0.0368

AC:

732

AN:

19906

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

533

1066

1600

2133

2666

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0305

AC:

4641

AN:

152212

Hom.:

Cov.:

AF XY:

0.0297

AC XY:

2207

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.00857

AC:

356

AN:

41546

American (AMR)

AF:

0.0365

AC:

558

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.0487

AC:

169

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5182

South Asian (SAS)

AF:

0.00828

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0357

AC:

378

AN:

10580

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0438

AC:

2982

AN:

68016

Other (OTH)

AF:

0.0389

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

230

460

690

920

1150

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0375

Hom.:

Bravo

AF:

0.0302

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

8.4

(source)

DANN

Benign

0.75

PhyloP100

0.89

Mutation Taster

=100/0

polymorphism

(source)

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

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rs12829218

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over