Genetic Variant PPP1CB-DT:n.123A>G (chr2-28751600-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000653462.1(PPP1CB-DT):n.123A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.666 in 161,858 control chromosomes in the GnomAD database, including 36,281 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.67 ( 34223 hom., cov: 36)

Exomes 𝑓: 0.64 ( 2058 hom. )

Consequence

PPP1CB-DT
ENST00000653462.1 non_coding_transcript_exon

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.14

Variant links:

Genes affected

PPP1CB-DT (HGNC:55829): (PPP1CB divergent transcript)

PPP1CB-DT links:

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 was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 2-28751600-T-C is Benign according to our data. Variant chr2-28751600-T-C is described in ClinVar as [Benign]. Clinvar id is 1261656.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.716 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1CB	NM_002709.3 link	c.-525T>C		upstream_gene_variant		ENST00000395366.3	NP_002700.1	P62140V9HW04

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1CB	ENST00000395366.3 link	c.-525T>C		upstream_gene_variant		1	NM_002709.3	ENSP00000378769.2		P62140

Frequencies

GnomAD3 genomes

AF:

0.668

AC:

101622

AN:

152120

Hom.:

34203

Cov.:

show subpopulations

Gnomad AFR

AF:

0.602

Gnomad AMI

AF:

0.503

Gnomad AMR

AF:

0.685

Gnomad ASJ

AF:

0.653

Gnomad EAS

AF:

0.722

Gnomad SAS

AF:

0.736

Gnomad FIN

AF:

0.705

Gnomad MID

AF:

0.699

Gnomad NFE

AF:

0.692

Gnomad OTH

AF:

0.697

GnomAD4 exome

AF:

0.643

AC:

6188

AN:

9620

Hom.:

2058

Cov.:

AF XY:

0.640

AC XY:

3328

AN XY:

5204

show subpopulations

African (AFR)

AF:

0.620

AC:

AN:

American (AMR)

AF:

0.650

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.516

AC:

AN:

182

East Asian (EAS)

AF:

0.618

AC:

AN:

South Asian (SAS)

AF:

0.669

AC:

1293

AN:

1932

European-Finnish (FIN)

AF:

0.639

AC:

327

AN:

512

Middle Eastern (MID)

AF:

0.567

AC:

AN:

European-Non Finnish (NFE)

AF:

0.638

AC:

4007

AN:

6278

Other (OTH)

AF:

0.662

AC:

372

AN:

562

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

199

298

398

497

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.668

AC:

101686

AN:

152238

Hom.:

34223

Cov.:

AF XY:

0.671

AC XY:

49954

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.602

AC:

25011

AN:

41548

American (AMR)

AF:

0.685

AC:

10472

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.653

AC:

2268

AN:

3472

East Asian (EAS)

AF:

0.722

AC:

3732

AN:

5166

South Asian (SAS)

AF:

0.736

AC:

3557

AN:

4832

European-Finnish (FIN)

AF:

0.705

AC:

7475

AN:

10602

Middle Eastern (MID)

AF:

0.687

AC:

202

AN:

294

European-Non Finnish (NFE)

AF:

0.692

AC:

47033

AN:

68012

Other (OTH)

AF:

0.700

AC:

1478

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1868

3736

5605

7473

9341

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.674

Hom.:

4317

Bravo

AF:

0.663

Asia WGS

AF:

0.745

AC:

2591

AN:

3478

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

- -

Oct 01, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

8.1

(source)

DANN

Benign

0.43

PhyloP100

-2.1

PromoterAI

0.046

Neutral

(source)

Splicing

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

Publications

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2-28751600-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over