rs10160951

Variant names:

Variant summary

Our verdict is . The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

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

new If you want to explore the variant's impact on the transcript NM_002562.6, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.124).

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002562.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
P2RX7	NM_002562.6	MANE Select	c.1289C>G	p.Pro430Arg	missense splice_region	Exon 12 of 13	NP_002553.3
P2RX7	NR_033948.2		n.1607C>G		splice_region non_coding_transcript_exon	Exon 12 of 13
P2RX7	NR_033949.2		n.1523C>G		splice_region non_coding_transcript_exon	Exon 13 of 14

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
P2RX7	ENST00000328963.10	TSL:1 MANE Select	c.1289C>G	p.Pro430Arg	missense splice_region	Exon 12 of 13	ENSP00000330696.6	Q99572-1
P2RX7	ENST00000261826.10	TSL:1	n.*742C>G		3_prime_UTR	Exon 11 of 12	ENSP00000261826.6	J3KN30
P2RX7	ENST00000538011.5	TSL:1	n.*1044C>G		3_prime_UTR	Exon 13 of 14	ENSP00000439247.1	F5H2X6

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

Asia WGS

AF:

0.00953

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over