dbSNP rs208290: P2RX7:c.363+106G>A (chr12-121156253-G-A) – 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.363+106G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 867,118 control chromosomes in the GnomAD database, including 54,764 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 0.42 ( 16894 hom., cov: 31)

Exomes 𝑓: 0.31 ( 37870 hom. )

Consequence

P2RX7
NM_002562.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.464

Publications

7 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:

LOC105370032 (HGNC:):

LOC105370032 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=-0.96).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RX7	NM_002562.6 link	c.363+106G>A		intron_variant	Intron 3 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.363+106G>A		intron_variant	Intron 3 of 12	1	NM_002562.6	ENSP00000330696.6		Q99572-1

Frequencies

GnomAD3 genomes

AF:

0.420

AC:

63802

AN:

151910

Hom.:

16833

Cov.:

show subpopulations

Gnomad AFR

AF:

0.755

Gnomad AMI

AF:

0.214

Gnomad AMR

AF:

0.248

Gnomad ASJ

AF:

0.215

Gnomad EAS

AF:

0.378

Gnomad SAS

AF:

0.391

Gnomad FIN

AF:

0.388

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.282

Gnomad OTH

AF:

0.343

GnomAD4 exome

AF:

0.311

AC:

222228

AN:

715090

Hom.:

37870

AF XY:

0.312

AC XY:

118396

AN XY:

379786

show subpopulations

African (AFR)

AF:

0.760

AC:

14252

AN:

18754

American (AMR)

AF:

0.177

AC:

6454

AN:

36386

Ashkenazi Jewish (ASJ)

AF:

0.214

AC:

4195

AN:

19568

East Asian (EAS)

AF:

0.380

AC:

13565

AN:

35736

South Asian (SAS)

AF:

0.386

AC:

25789

AN:

66806

European-Finnish (FIN)

AF:

0.393

AC:

20036

AN:

50922

Middle Eastern (MID)

AF:

0.234

AC:

620

AN:

2646

European-Non Finnish (NFE)

AF:

0.281

AC:

126161

AN:

449178

Other (OTH)

AF:

0.318

AC:

11156

AN:

35094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

6967

13933

20900

27866

34833

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2270

4540

6810

9080

11350

<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:

0.421

AC:

63940

AN:

152028

Hom.:

16894

Cov.:

AF XY:

0.418

AC XY:

31080

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.755

AC:

31306

AN:

41458

American (AMR)

AF:

0.249

AC:

3804

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.215

AC:

745

AN:

3470

East Asian (EAS)

AF:

0.377

AC:

1944

AN:

5154

South Asian (SAS)

AF:

0.393

AC:

1892

AN:

4816

European-Finnish (FIN)

AF:

0.388

AC:

4100

AN:

10560

Middle Eastern (MID)

AF:

0.187

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.282

AC:

19173

AN:

67970

Other (OTH)

AF:

0.344

AC:

726

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1535

3070

4605

6140

7675

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

560

1120

1680

2240

2800

<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:

0.340

Hom.:

4231

Bravo

AF:

0.420

Asia WGS

AF:

0.412

AC:

1434

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.40

(source)

DANN

Benign

0.56

PhyloP100

-0.46

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