dbSNP rs12815078: P2RX7:c.1291-101A>G (chr12-121184204-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002562.6(P2RX7):c.1291-101A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.079 in 1,372,304 control chromosomes in the GnomAD database, including 4,679 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 0.067 ( 370 hom., cov: 32)

Exomes 𝑓: 0.081 ( 4309 hom. )

Consequence

P2RX7
NM_002562.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.25

Publications

4 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=-0.97).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RX7	NM_002562.6 link	c.1291-101A>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.1291-101A>G		intron_variant	Intron 12 of 12	1	NM_002562.6	ENSP00000330696.6		Q99572-1

Frequencies

GnomAD3 genomes

AF:

0.0669

AC:

10176

AN:

152206

Hom.:

370

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0373

Gnomad AMI

AF:

0.175

Gnomad AMR

AF:

0.0631

Gnomad ASJ

AF:

0.0614

Gnomad EAS

AF:

0.0630

Gnomad SAS

AF:

0.0403

Gnomad FIN

AF:

0.0618

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0872

Gnomad OTH

AF:

0.0788

GnomAD4 exome

AF:

0.0805

AC:

98219

AN:

1219980

Hom.:

4309

AF XY:

0.0799

AC XY:

47880

AN XY:

599084

show subpopulations

African (AFR)

AF:

0.0340

AC:

908

AN:

26730

American (AMR)

AF:

0.0498

AC:

1293

AN:

25966

Ashkenazi Jewish (ASJ)

AF:

0.0675

AC:

1279

AN:

18946

East Asian (EAS)

AF:

0.0569

AC:

2073

AN:

36424

South Asian (SAS)

AF:

0.0447

AC:

2665

AN:

59652

European-Finnish (FIN)

AF:

0.0609

AC:

2061

AN:

33854

Middle Eastern (MID)

AF:

0.0618

AC:

226

AN:

3656

European-Non Finnish (NFE)

AF:

0.0869

AC:

83716

AN:

963514

Other (OTH)

AF:

0.0780

AC:

3998

AN:

51238

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

4399

8797

13196

17594

21993

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3056

6112

9168

12224

15280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0668

AC:

10176

AN:

152324

Hom.:

370

Cov.:

AF XY:

0.0644

AC XY:

4794

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.0372

AC:

1548

AN:

41574

American (AMR)

AF:

0.0628

AC:

960

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0614

AC:

213

AN:

3470

East Asian (EAS)

AF:

0.0626

AC:

325

AN:

5194

South Asian (SAS)

AF:

0.0405

AC:

196

AN:

4834

European-Finnish (FIN)

AF:

0.0618

AC:

656

AN:

10622

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0872

AC:

5934

AN:

68020

Other (OTH)

AF:

0.0784

AC:

166

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

503

1007

1510

2014

2517

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

118

236

354

472

590

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0770

Hom.:

260

Bravo

AF:

0.0660

Asia WGS

AF:

0.0590

AC:

203

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

0.012

(source)

DANN

Benign

0.21

PhyloP100

-2.2

Mutation Taster

=100/0

polymorphism (auto)

(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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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