2-28751425-T-C

Variant names:

• chr2-28751425-T-C
• rs149468963
• ENST00000653462.1:n.298A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000653462.1(PPP1CB-DT):​n.298A>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 0.00547 in 152,310 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0055 (7 hom., cov: 34)
• Consequence: PPP1CB-DT ENST00000653462.1 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.410

Genes affected

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

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

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 2-28751425-T-C is Benign according to our data. Variant chr2-28751425-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1186254.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00547 (833/152310) while in subpopulation AFR AF = 0.0189 (787/41568). AF 95% confidence interval is 0.0178. There are 7 homozygotes in GnomAd4. There are 384 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1CB-DT	XR_001739359.2	n.75A>G		non_coding_transcript_exon_variant	Exon 1 of 5
PPP1CB-DT	XR_001739360.2	n.75A>G		non_coding_transcript_exon_variant	Exon 1 of 6
PPP1CB-DT	XR_001739364.2	n.75A>G		non_coding_transcript_exon_variant	Exon 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1CB-DT	ENST00000653462.1	n.298A>G		non_coding_transcript_exon_variant	Exon 1 of 4
PPP1CB-DT	ENST00000658445.1	n.166A>G		non_coding_transcript_exon_variant	Exon 1 of 5
PPP1CB-DT	ENST00000665023.2	n.250A>G		non_coding_transcript_exon_variant	Exon 1 of 4

Frequencies

GnomAD3 genomes AF: 0.00546 AC: 831 AN: 152194 Hom.: 7 Cov.: 34

Gnomad AFR AF: 0.0189

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00382

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00547 AC: 833 AN: 152310 Hom.: 7 Cov.: 34 AF XY: 0.00516 AC XY: 384 AN XY: 74474

African (AFR) AF: 0.0189 AC: 787 AN: 41568

American (AMR) AF: 0.00216 AC: 33 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68032

Other (OTH) AF: 0.00378 AC: 8 AN: 2116

Alfa AF: 0.00500 Hom.: 0

Bravo AF: 0.00598

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Sep 29, 2019

GeneDx

Significance: Likely 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	-0.85
CADD	Benign	11
DANN	Benign	0.51
PhyloP100		0.41
PromoterAI		-0.0059	Neutral

Splicing

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

Publications

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Other links and lift over

dbSNP: rs149468963; hg19: chr2-28974291;