Variant 2-28752031-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The ENST00000296122.10(PPP1CB):c.-87-7C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0018 in 1,230,904 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0019 ( 2 hom. )

Consequence

PPP1CB
ENST00000296122.10 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.004835

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.35

Variant links:

Genes affected

PPP1CB (HGNC:9282): (protein phosphatase 1 catalytic subunit beta) The protein encoded by this gene is one of the three catalytic subunits of protein phosphatase 1 (PP1). PP1 is a serine/threonine specific protein phosphatase known to be involved in the regulation of a variety of cellular processes, such as cell division, glycogen metabolism, muscle contractility, protein synthesis, and HIV-1 viral transcription. Mouse studies suggest that PP1 functions as a suppressor of learning and memory. Two alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

PPP1CB links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.28).

BP6

Variant 2-28752031-C-T is Benign according to our data. Variant chr2-28752031-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1203931.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 196 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP1CB	NM_002709.3 linkuse as main transcript	c.-94C>T		5_prime_UTR_variant	1/8	ENST00000395366.3
PPP1CB	NM_206876.2 linkuse as main transcript	c.-87-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP1CB	ENST00000395366.3 linkuse as main transcript	c.-94C>T		5_prime_UTR_variant	1/8	1	NM_002709.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00129

AC:

196

AN:

152034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000459

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000755

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00221

Gnomad OTH

AF:

0.00191

GnomAD4 exome

AF:

0.00187

AC:

2016

AN:

1078754

Hom.:

Cov.:

AF XY:

0.00181

AC XY:

990

AN XY:

545602

show subpopulations

Gnomad4 AFR exome

AF:

0.000283

Gnomad4 AMR exome

AF:

0.000767

Gnomad4 ASJ exome

AF:

0.000604

Gnomad4 EAS exome

AF:

0.0000891

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000435

Gnomad4 NFE exome

AF:

0.00240

Gnomad4 OTH exome

AF:

0.00108

GnomAD4 genome

AF:

0.00129

AC:

196

AN:

152150

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.000458

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000755

Gnomad4 NFE

AF:

0.00221

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000583

Hom.:

Bravo

AF:

0.00135

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 24, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.96

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0048

dbscSNV1_RF

Benign

0.058

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