2-28752031-C-T

Position:

• chr2-28752031-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_206876.2(PPP1CB):​c.-87-7C>T variant causes a splice region, 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 NM_206876.2 splice_region, intron
• Scores: Splicing: ADA: 0.004835
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.35

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]

ACMG classification

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	Protein	UniProt
PPP1CB	NM_002709.3	c.-94C>T		5_prime_UTR_variant	1/8	ENST00000395366.3	NP_002700.1
PPP1CB	NM_206876.2	c.-87-7C>T		splice_region_variant, intron_variant			NP_996759.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP1CB	ENST00000395366	c.-94C>T		5_prime_UTR_variant	1/8	1	NM_002709.3	ENSP00000378769.2

Frequencies

GnomAD3 genomes AF: 0.00129 AC: 196 AN: 152034 Hom.: 0 Cov.: 30

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.: 2 Cov.: 14 AF XY: 0.00181 AC XY: 990 AN XY: 545602

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.: 0 Cov.: 30 AF XY: 0.00106 AC XY: 79 AN XY: 74390

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.: 0

Bravo AF: 0.00135

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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	21
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

Other links and lift over

dbSNP: rs530957503; hg19: chr2-28974897; COSMIC: COSV56090066;