dbSNP rs10160951: P2RX7:p.Pro430Arg (chr12-121180454-C-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.1289C>G(p.Pro430Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00932 in 1,517,598 control chromosomes in the GnomAD database, including 812 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P430T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.042 ( 408 hom., cov: 31)

Exomes 𝑓: 0.0057 ( 404 hom. )

Consequence

P2RX7
NM_002562.6 missense, splice_region

Scores

Splicing: ADA: 0.05033

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.797

Publications

12 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 (MetaRNN=0.0018902719).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RX7	NM_002562.6 link	c.1289C>G	p.Pro430Arg	missense_variant, splice_region_variant	Exon 12 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.1289C>G	p.Pro430Arg	missense_variant, splice_region_variant	Exon 12 of 13	1	NM_002562.6	ENSP00000330696.6		Q99572-1

Frequencies

GnomAD3 genomes

AF:

0.0422

AC:

6380

AN:

151036

Hom.:

409

Cov.:

show subpopulations

Gnomad AFR

AF:

0.141

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0210

Gnomad ASJ

AF:

0.00260

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000627

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0478

Gnomad NFE

AF:

0.00231

Gnomad OTH

AF:

0.0352

GnomAD2 exomes

AF:

0.0136

AC:

2930

AN:

215124

AF XY:

0.0103

show subpopulations

Gnomad AFR exome

AF:

0.148

Gnomad AMR exome

AF:

0.0129

Gnomad ASJ exome

AF:

0.00275

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00240

Gnomad OTH exome

AF:

0.0122

GnomAD4 exome

AF:

0.00568

AC:

7755

AN:

1366464

Hom.:

404

Cov.:

AF XY:

0.00516

AC XY:

3524

AN XY:

683250

show subpopulations

African (AFR)

AF:

0.152

AC:

4506

AN:

29612

American (AMR)

AF:

0.0139

AC:

458

AN:

33062

Ashkenazi Jewish (ASJ)

AF:

0.00274

AC:

AN:

24080

East Asian (EAS)

AF:

0.00

AC:

AN:

38996

South Asian (SAS)

AF:

0.000924

AC:

AN:

77892

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52450

Middle Eastern (MID)

AF:

0.0451

AC:

246

AN:

5458

European-Non Finnish (NFE)

AF:

0.00157

AC:

1650

AN:

1048330

Other (OTH)

AF:

0.0134

AC:

757

AN:

56584

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

302

604

907

1209

1511

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

182

364

546

728

910

<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:

0.0423

AC:

6387

AN:

151134

Hom.:

408

Cov.:

AF XY:

0.0399

AC XY:

2943

AN XY:

73766

show subpopulations

African (AFR)

AF:

0.141

AC:

5814

AN:

41186

American (AMR)

AF:

0.0209

AC:

317

AN:

15164

Ashkenazi Jewish (ASJ)

AF:

0.00260

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.000419

AC:

AN:

4772

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10240

Middle Eastern (MID)

AF:

0.0517

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00231

AC:

157

AN:

67856

Other (OTH)

AF:

0.0348

AC:

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

279

558

838

1117

1396

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

186

248

310

<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:

0.00833

Hom.:

Bravo

AF:

0.0483

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.138

AC:

607

ESP6500EA

AF:

0.00302

AC:

ExAC

AF:

0.0145

AC:

1765

Asia WGS

AF:

0.00953

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Uncertain

0.0

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

Eigen

Benign

0.078

Eigen_PC

Benign

0.091

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.73

MetaRNN

Benign

0.0019

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.6

PhyloP100

0.80

PrimateAI

Benign

0.31

REVEL

Benign

0.12

Sift4G

Benign

0.26

Polyphen

0.26

Vest4

0.081

ClinPred

0.013

GERP RS

4.7

Varity_R

0.11

gMVP

0.23

Mutation Taster

=66/34

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.050

dbscSNV1_RF

Benign

0.37

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