Variant 17-39635843-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_032192.4(PPP1R1B):c.593C>A(p.Ser198Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 1,613,446 control chromosomes in the GnomAD database, including 124 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0067 ( 6 hom., cov: 32)

Exomes 𝑓: 0.011 ( 118 hom. )

Consequence

PPP1R1B
NM_032192.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0750

Variant links:

Genes affected

PPP1R1B (HGNC:9287): (protein phosphatase 1 regulatory inhibitor subunit 1B) This gene encodes a bifunctional signal transduction molecule. Dopaminergic and glutamatergic receptor stimulation regulates its phosphorylation and function as a kinase or phosphatase inhibitor. As a target for dopamine, this gene may serve as a therapeutic target for neurologic and psychiatric disorders. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

PPP1R1B links:

LOC124903998 (HGNC:):

LOC124903998 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003179282).

BP6

Variant 17-39635843-C-A is Benign according to our data. Variant chr17-39635843-C-A is described in ClinVar as [Benign]. Clinvar id is 775160.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP1R1B	NM_032192.4 linkuse as main transcript	c.593C>A	p.Ser198Tyr	missense_variant	7/7	ENST00000254079.9
LOC124903998	XR_007065749.1 linkuse as main transcript	n.301-817G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP1R1B	ENST00000254079.9 linkuse as main transcript	c.593C>A	p.Ser198Tyr	missense_variant	7/7	1	NM_032192.4	P1	Q9UD71-1

Frequencies

GnomAD3 genomes

AF:

0.00674

AC:

1025

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00179

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00497

Gnomad ASJ

AF:

0.0138

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00678

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0107

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00731

AC:

1833

AN:

250802

Hom.:

AF XY:

0.00755

AC XY:

1024

AN XY:

135598

show subpopulations

Gnomad AFR exome

AF:

0.00173

Gnomad AMR exome

AF:

0.00318

Gnomad ASJ exome

AF:

0.0156

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00160

Gnomad FIN exome

AF:

0.00661

Gnomad NFE exome

AF:

0.0114

Gnomad OTH exome

AF:

0.00850

GnomAD4 exome

AF:

0.0106

AC:

15435

AN:

1461152

Hom.:

118

Cov.:

AF XY:

0.0103

AC XY:

7504

AN XY:

726836

show subpopulations

Gnomad4 AFR exome

AF:

0.00134

Gnomad4 AMR exome

AF:

0.00338

Gnomad4 ASJ exome

AF:

0.0148

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00219

Gnomad4 FIN exome

AF:

0.00630

Gnomad4 NFE exome

AF:

0.0123

Gnomad4 OTH exome

AF:

0.00983

GnomAD4 genome

AF:

0.00672

AC:

1024

AN:

152294

Hom.:

Cov.:

AF XY:

0.00645

AC XY:

480

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00178

Gnomad4 AMR

AF:

0.00497

Gnomad4 ASJ

AF:

0.0138

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.00678

Gnomad4 NFE

AF:

0.0107

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.00938

Hom.:

Bravo

AF:

0.00660

TwinsUK

AF:

0.0173

AC:

ALSPAC

AF:

0.0109

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.0109

AC:

ExAC

AF:

0.00711

AC:

863

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0105

EpiControl

AF:

0.0119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.59

Cadd

Benign

Dann

Benign

0.93

DEOGEN2

Benign

0.21

T;T;.;.;.

Eigen

Benign

-0.99

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.022

MetaRNN

Benign

0.0032

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;N;.;.;.

MutationTaster

Benign

1.0

N;N;N;N;N;N;N

PrimateAI

Benign

0.33

Sift4G

Benign

0.081

T;T;T;D;D

Polyphen

0.14

B;B;.;.;.

Vest4

0.25

MVP

0.12

MPC

0.55

ClinPred

0.0016

GERP RS

-3.1

Varity_R

0.057

gMVP

0.026

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

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