Variant rs35933842 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 1P and 12B. PP3BP6_Very_StrongBS2

The NM_002562.6(P2RX7):c.125+1G>T variant causes a splice donor, intron change. The variant allele was found at a frequency of 0.00726 in 1,614,138 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0053 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0075 ( 55 hom. )

Consequence

P2RX7
NM_002562.6 splice_donor, intron

Scores

Splicing: ADA: 1.000

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2O:1

Conservation

PhyloP100: 4.22

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:

LOC105370032 (HGNC:):

LOC105370032 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 5: Cadd, dbscSNV1_ADA, dbscSNV1_RF, max_spliceai, Eigen [when BayesDel_addAF, MutationTaster was below the threshold]

BP6

Variant 12-121133096-G-T is Benign according to our data. Variant chr12-121133096-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 489390.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RX7	NM_002562.6 link	c.125+1G>T		splice_donor_variant, intron_variant	Intron 1 of 12	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.125+1G>T		splice_donor_variant, intron_variant	Intron 1 of 12	1	NM_002562.6	ENSP00000330696.6		Q99572-1

Frequencies

GnomAD3 genomes

AF:

0.00528

AC:

804

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00157

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00595

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00235

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00861

Gnomad OTH

AF:

0.00670

GnomAD3 exomes

AF:

0.00553

AC:

1390

AN:

251402

Hom.:

AF XY:

0.00575

AC XY:

781

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00474

Gnomad ASJ exome

AF:

0.00536

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00121

Gnomad FIN exome

AF:

0.00240

Gnomad NFE exome

AF:

0.00886

Gnomad OTH exome

AF:

0.00896

GnomAD4 exome

AF:

0.00747

AC:

10921

AN:

1461788

Hom.:

Cov.:

AF XY:

0.00735

AC XY:

5344

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.00119

Gnomad4 AMR exome

AF:

0.00496

Gnomad4 ASJ exome

AF:

0.00482

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00118

Gnomad4 FIN exome

AF:

0.00268

Gnomad4 NFE exome

AF:

0.00885

Gnomad4 OTH exome

AF:

0.00649

GnomAD4 genome

AF:

0.00526

AC:

802

AN:

152350

Hom.:

Cov.:

AF XY:

0.00510

AC XY:

380

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.00156

Gnomad4 AMR

AF:

0.00595

Gnomad4 ASJ

AF:

0.00519

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00235

Gnomad4 NFE

AF:

0.00860

Gnomad4 OTH

AF:

0.00663

Alfa

AF:

0.00757

Hom.:

Bravo

AF:

0.00556

TwinsUK

AF:

0.0146

AC:

ALSPAC

AF:

0.00752

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.0102

AC:

ExAC

AF:

0.00539

AC:

654

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00911

EpiControl

AF:

0.00865

ClinVar

Significance: Likely benign

Submissions summary: Benign:2Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2Other:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

GenomeConnect, ClinGen

Significance: not provided

Review Status: no classification provided

Collection Method: phenotyping only

GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.088

BayesDel_noAF

Uncertain

0.11

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Pathogenic

0.97

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Uncertain

0.89

GERP RS

4.5

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.93

SpliceAI score (max)

0.99

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.99

Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over