dbSNP rs3751144: P2RX7:p.Pro474Pro (chr12-121184436-C-T) – 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.1422C>T(p.Pro474Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0969 in 1,613,982 control chromosomes in the GnomAD database, including 10,364 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 0.12 ( 1436 hom., cov: 32)

Exomes 𝑓: 0.094 ( 8928 hom. )

Consequence

P2RX7
NM_002562.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -6.23

Publications

19 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP7

Synonymous conserved (PhyloP=-6.23 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RX7	NM_002562.6 link	c.1422C>T	p.Pro474Pro	synonymous_variant	Exon 13 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.1422C>T	p.Pro474Pro	synonymous_variant	Exon 13 of 13	1	NM_002562.6	ENSP00000330696.6		Q99572-1

Frequencies

GnomAD3 genomes

AF:

0.122

AC:

18565

AN:

152040

Hom.:

1424

Cov.:

show subpopulations

Gnomad AFR

AF:

0.157

Gnomad AMI

AF:

0.0308

Gnomad AMR

AF:

0.220

Gnomad ASJ

AF:

0.0554

Gnomad EAS

AF:

0.162

Gnomad SAS

AF:

0.162

Gnomad FIN

AF:

0.128

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0777

Gnomad OTH

AF:

0.100

GnomAD2 exomes

AF:

0.141

AC:

35400

AN:

251364

AF XY:

0.131

show subpopulations

Gnomad AFR exome

AF:

0.156

Gnomad AMR exome

AF:

0.359

Gnomad ASJ exome

AF:

0.0587

Gnomad EAS exome

AF:

0.173

Gnomad FIN exome

AF:

0.126

Gnomad NFE exome

AF:

0.0751

Gnomad OTH exome

AF:

0.113

GnomAD4 exome

AF:

0.0942

AC:

137726

AN:

1461824

Hom.:

8928

Cov.:

AF XY:

0.0939

AC XY:

68274

AN XY:

727222

show subpopulations

African (AFR)

AF:

0.153

AC:

5116

AN:

33480

American (AMR)

AF:

0.338

AC:

15132

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.0601

AC:

1571

AN:

26136

East Asian (EAS)

AF:

0.156

AC:

6182

AN:

39700

South Asian (SAS)

AF:

0.150

AC:

12936

AN:

86256

European-Finnish (FIN)

AF:

0.127

AC:

6768

AN:

53400

Middle Eastern (MID)

AF:

0.0638

AC:

368

AN:

5768

European-Non Finnish (NFE)

AF:

0.0752

AC:

83607

AN:

1111978

Other (OTH)

AF:

0.100

AC:

6046

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

6953

13906

20860

27813

34766

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3368

6736

10104

13472

16840

<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:

0.122

AC:

18609

AN:

152158

Hom.:

1436

Cov.:

AF XY:

0.126

AC XY:

9374

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.157

AC:

6508

AN:

41518

American (AMR)

AF:

0.221

AC:

3369

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.0554

AC:

192

AN:

3468

East Asian (EAS)

AF:

0.163

AC:

841

AN:

5160

South Asian (SAS)

AF:

0.162

AC:

782

AN:

4824

European-Finnish (FIN)

AF:

0.128

AC:

1359

AN:

10598

Middle Eastern (MID)

AF:

0.0782

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0777

AC:

5284

AN:

68012

Other (OTH)

AF:

0.106

AC:

223

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

803

1606

2408

3211

4014

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

204

408

612

816

1020

<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:

0.0937

Hom.:

3434

Bravo

AF:

0.131

Asia WGS

AF:

0.180

AC:

627

AN:

3478

EpiCase

AF:

0.0671

EpiControl

AF:

0.0708

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.058

(source)

DANN

Benign

0.84

PhyloP100

-6.2

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