dbSNP rs1653598: P2RX7:c.1188+34T>C (chr12-121177480-T-C) – 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.1188+34T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 1,601,268 control chromosomes in the GnomAD database, including 122,237 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 0.39 ( 11875 hom., cov: 31)

Exomes 𝑓: 0.39 ( 110362 hom. )

Consequence

P2RX7
NM_002562.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.610

Publications

9 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:

ENSG00000295862 (HGNC:):

ENSG00000295862 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=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RX7	NM_002562.6 link	c.1188+34T>C		intron_variant	Intron 11 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.1188+34T>C		intron_variant	Intron 11 of 12	1	NM_002562.6	ENSP00000330696.6		Q99572-1

Frequencies

GnomAD3 genomes

AF:

0.388

AC:

58830

AN:

151774

Hom.:

11854

Cov.:

show subpopulations

Gnomad AFR

AF:

0.446

Gnomad AMI

AF:

0.396

Gnomad AMR

AF:

0.243

Gnomad ASJ

AF:

0.344

Gnomad EAS

AF:

0.127

Gnomad SAS

AF:

0.369

Gnomad FIN

AF:

0.448

Gnomad MID

AF:

0.278

Gnomad NFE

AF:

0.400

Gnomad OTH

AF:

0.364

GnomAD2 exomes

AF:

0.349

AC:

87301

AN:

250324

AF XY:

0.357

show subpopulations

Gnomad AFR exome

AF:

0.458

Gnomad AMR exome

AF:

0.168

Gnomad ASJ exome

AF:

0.351

Gnomad EAS exome

AF:

0.111

Gnomad FIN exome

AF:

0.452

Gnomad NFE exome

AF:

0.394

Gnomad OTH exome

AF:

0.352

GnomAD4 exome

AF:

0.385

AC:

558517

AN:

1449376

Hom.:

110362

Cov.:

AF XY:

0.386

AC XY:

278559

AN XY:

721330

show subpopulations

African (AFR)

AF:

0.464

AC:

15420

AN:

33210

American (AMR)

AF:

0.179

AC:

8009

AN:

44652

Ashkenazi Jewish (ASJ)

AF:

0.354

AC:

9217

AN:

26046

East Asian (EAS)

AF:

0.139

AC:

5514

AN:

39622

South Asian (SAS)

AF:

0.402

AC:

34519

AN:

85916

European-Finnish (FIN)

AF:

0.447

AC:

23842

AN:

53370

Middle Eastern (MID)

AF:

0.362

AC:

1563

AN:

4318

European-Non Finnish (NFE)

AF:

0.397

AC:

437990

AN:

1102336

Other (OTH)

AF:

0.375

AC:

22443

AN:

59906

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

17025

34049

51074

68098

85123

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13480

26960

40440

53920

67400

<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:

0.388

AC:

58897

AN:

151892

Hom.:

11875

Cov.:

AF XY:

0.383

AC XY:

28412

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.446

AC:

18484

AN:

41416

American (AMR)

AF:

0.242

AC:

3699

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.344

AC:

1192

AN:

3468

East Asian (EAS)

AF:

0.126

AC:

653

AN:

5164

South Asian (SAS)

AF:

0.370

AC:

1777

AN:

4798

European-Finnish (FIN)

AF:

0.448

AC:

4719

AN:

10522

Middle Eastern (MID)

AF:

0.296

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.400

AC:

27169

AN:

67948

Other (OTH)

AF:

0.359

AC:

757

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1781

3562

5342

7123

8904

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

570

1140

1710

2280

2850

<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:

0.382

Hom.:

4449

Bravo

AF:

0.371

Asia WGS

AF:

0.270

AC:

941

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

5.7

(source)

DANN

Benign

0.16

PhyloP100

0.61

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