2-28751757-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_206876.2(PPP1CB):c.-151C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000633 in 312,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00056 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00070 (0 hom.)
• Consequence: PPP1CB NM_206876.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.316

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

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 2-28751757-C-G is Benign according to our data. Variant chr2-28751757-C-G is described in ClinVar as [Benign]. Clinvar id is 1182105.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 85 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP1CB-DT	XR_007086259.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP1CB	ENST00000420282.6	c.-114C>G		5_prime_UTR_variant	1/9	4		P1
PPP1CB	ENST00000441461.6	c.-151C>G		5_prime_UTR_variant	1/9	2		P1
PPP1CB	ENST00000455580.6	c.-96C>G		5_prime_UTR_variant	1/8	3

Frequencies

GnomAD3 genomes AF: 0.000559 AC: 85 AN: 152088 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000824

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00100 AC: 21 AN: 21002 Hom.: 0 AF XY: 0.00142 AC XY: 17 AN XY: 11942

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00240

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000573

Gnomad FIN exome AF: 0.00155

Gnomad NFE exome AF: 0.00135

Gnomad OTH exome AF: 0.00242

GnomAD4 exome AF: 0.000703 AC: 113 AN: 160832 Hom.: 0 Cov.: 0 AF XY: 0.000628 AC XY: 58 AN XY: 92420

Gnomad4 AFR exome AF: 0.000387

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00302

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000159

Gnomad4 FIN exome AF: 0.00146

Gnomad4 NFE exome AF: 0.000819

Gnomad4 OTH exome AF: 0.000370

GnomAD4 genome AF: 0.000559 AC: 85 AN: 152088 Hom.: 0 Cov.: 30 AF XY: 0.000579 AC XY: 43 AN XY: 74292

Gnomad4 AFR AF: 0.0000483

Gnomad4 AMR AF: 0.0000655

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00132

Gnomad4 NFE AF: 0.000824

Gnomad4 OTH AF: 0.000478

Alfa AF: 0.000212 Hom.: 0

Bravo AF: 0.000506

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 26, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	16
Dann	Benign	0.70

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

Other links and lift over

dbSNP: rs556879162; hg19: chr2-28974623; COSMIC: COSV104608931; COSMIC: COSV104608931;