Genetic Variant P2RX7:p.Leu320Pro (chr12-121175465-T-C) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PP3BP4_StrongBP6_Very_StrongBS2

The NM_002562.6(P2RX7):c.959T>C(p.Leu320Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000801 in 1,469,704 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0042 ( 7 hom., cov: 31)

Exomes 𝑓: 0.00041 ( 3 hom. )

Consequence

P2RX7
NM_002562.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.11

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 5: AlphaMissense, BayesDel_noAF, Cadd, Eigen, MutationAssessor [when max_spliceai, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.013779283).

BP6

Variant 12-121175465-T-C is Benign according to our data. Variant chr12-121175465-T-C is described in ClinVar as Benign. ClinVar VariationId is 716992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RX7	NM_002562.6 link	c.959T>C	p.Leu320Pro	missense_variant	Exon 9 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.959T>C	p.Leu320Pro	missense_variant	Exon 9 of 13	1	NM_002562.6	ENSP00000330696.6		Q99572-1

Frequencies

GnomAD3 genomes

AF:

0.00416

AC:

633

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0142

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00117

AC:

293

AN:

251442

AF XY:

0.000817

show subpopulations

Gnomad AFR exome

AF:

0.0150

Gnomad AMR exome

AF:

0.00121

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000412

AC:

543

AN:

1317442

Hom.:

Cov.:

AF XY:

0.000343

AC XY:

228

AN XY:

663818

show subpopulations

African (AFR)

AF:

0.0135

AC:

414

AN:

30656

American (AMR)

AF:

0.00128

AC:

AN:

44556

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25284

East Asian (EAS)

AF:

0.00

AC:

AN:

39060

South Asian (SAS)

AF:

0.00

AC:

AN:

83264

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53364

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5520

European-Non Finnish (NFE)

AF:

0.0000255

AC:

AN:

980100

Other (OTH)

AF:

0.000845

AC:

AN:

55638

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

123

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.00416

AC:

634

AN:

152262

Hom.:

Cov.:

AF XY:

0.00391

AC XY:

291

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.0142

AC:

590

AN:

41550

American (AMR)

AF:

0.00229

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68026

Other (OTH)

AF:

0.00332

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

102

136

170

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00142

Hom.:

Bravo

AF:

0.00495

ESP6500AA

AF:

0.0152

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00139

AC:

169

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0000546

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Apr 10, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Uncertain

0.043

BayesDel_noAF

Pathogenic

0.30

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.40

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.89

MetaRNN

Benign

0.014

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.5

PhyloP100

4.1

PrimateAI

Uncertain

0.72

REVEL

Uncertain

0.33

Sift4G

Uncertain

0.0040

Polyphen

1.0

Vest4

0.92

MVP

0.85

ClinPred

0.090

GERP RS

5.8

Varity_R

0.46

gMVP

0.85

Mutation Taster

=55/45

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over