Genetic Variant P2RX7:p.Val154Val (chr12-121162449-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_002562.6(P2RX7):c.462G>A(p.Val154Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0138 in 1,613,892 control chromosomes in the GnomAD database, including 744 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 0.038 ( 290 hom., cov: 32)

Exomes 𝑓: 0.011 ( 454 hom. )

Consequence

P2RX7
NM_002562.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.43

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP7

Synonymous conserved (PhyloP=-2.43 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RX7	NM_002562.6 link	c.462G>A	p.Val154Val	synonymous_variant	Exon 5 of 13	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.462G>A	p.Val154Val	synonymous_variant	Exon 5 of 13	1	NM_002562.6	ENSP00000330696.6		Q99572-1

Frequencies

GnomAD3 genomes

AF:

0.0383

AC:

5819

AN:

152110

Hom.:

291

Cov.:

show subpopulations

Gnomad AFR

AF:

0.116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0141

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0472

Gnomad FIN

AF:

0.0107

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.00556

Gnomad OTH

AF:

0.0330

GnomAD2 exomes

AF:

0.0185

AC:

4645

AN:

251112

AF XY:

0.0183

show subpopulations

Gnomad AFR exome

AF:

0.120

Gnomad AMR exome

AF:

0.00900

Gnomad ASJ exome

AF:

0.00645

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00865

Gnomad NFE exome

AF:

0.00570

Gnomad OTH exome

AF:

0.0148

GnomAD4 exome

AF:

0.0112

AC:

16374

AN:

1461662

Hom.:

454

Cov.:

AF XY:

0.0120

AC XY:

8710

AN XY:

727122

show subpopulations

African (AFR)

AF:

0.125

AC:

4169

AN:

33478

American (AMR)

AF:

0.00961

AC:

430

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00624

AC:

163

AN:

26134

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39700

South Asian (SAS)

AF:

0.0441

AC:

3807

AN:

86250

European-Finnish (FIN)

AF:

0.00777

AC:

414

AN:

53248

Middle Eastern (MID)

AF:

0.0238

AC:

137

AN:

5768

European-Non Finnish (NFE)

AF:

0.00566

AC:

6289

AN:

1111972

Other (OTH)

AF:

0.0159

AC:

962

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

796

1592

2387

3183

3979

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

340

680

1020

1360

1700

<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:

0.0382

AC:

5821

AN:

152230

Hom.:

290

Cov.:

AF XY:

0.0375

AC XY:

2789

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.115

AC:

4793

AN:

41516

American (AMR)

AF:

0.0141

AC:

215

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00432

AC:

AN:

3470

East Asian (EAS)

AF:

0.000579

AC:

AN:

5184

South Asian (SAS)

AF:

0.0466

AC:

225

AN:

4828

European-Finnish (FIN)

AF:

0.0107

AC:

113

AN:

10610

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00556

AC:

378

AN:

68016

Other (OTH)

AF:

0.0326

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

269

539

808

1078

1347

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

192

256

320

<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:

0.0253

Hom.:

Bravo

AF:

0.0417

Asia WGS

AF:

0.0270

AC:

AN:

3478

EpiCase

AF:

0.00627

EpiControl

AF:

0.00622

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.22

(source)

DANN

Benign

0.66

PhyloP100

-2.4

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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