Variant 2-28751664-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The XR_007086259.1(PPP1CB-DT):n.93T>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 0.0123 in 184,138 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 47 hom., cov: 31)

Exomes 𝑓: 0.0031 ( 0 hom. )

Consequence

PPP1CB-DT
XR_007086259.1 non_coding_transcript_exon

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.84

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 2-28751664-A-C is Benign according to our data. Variant chr2-28751664-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 1191835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0142 (2169/152302) while in subpopulation AFR AF= 0.0403 (1675/41580). AF 95% confidence interval is 0.0387. There are 47 homozygotes in gnomad4. There are 1098 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 47 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP1CB-DT	XR_007086259.1 linkuse as main transcript	n.93T>G		non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	Protein	Appris
PPP1CB	ENST00000455580.6 linkuse as main transcript	c.-189A>C	5_prime_UTR_variant	1/8	3	ENSP00000390715
PPP1CB-DT	ENST00000653462.1 linkuse as main transcript	n.59T>G	non_coding_transcript_exon_variant	1/4
PPP1CB	ENST00000420282.6 linkuse as main transcript		upstream_gene_variant		4	ENSP00000398839	P1
PPP1CB-DT	ENST00000665023.1 linkuse as main transcript		upstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.0143

AC:

2171

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0404

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00497

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00393

Gnomad FIN

AF:

0.0197

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00231

Gnomad OTH

AF:

0.00622

GnomAD4 exome

AF:

0.00308

AC:

AN:

31836

Hom.:

Cov.:

AF XY:

0.00223

AC XY:

AN XY:

17920

show subpopulations

Gnomad4 AFR exome

AF:

0.0469

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00148

Gnomad4 FIN exome

AF:

0.0104

Gnomad4 NFE exome

AF:

0.00224

Gnomad4 OTH exome

AF:

0.00788

GnomAD4 genome

AF:

0.0142

AC:

2169

AN:

152302

Hom.:

Cov.:

AF XY:

0.0147

AC XY:

1098

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0403

Gnomad4 AMR

AF:

0.00490

Gnomad4 ASJ

AF:

0.00576

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00373

Gnomad4 FIN

AF:

0.0197

Gnomad4 NFE

AF:

0.00231

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.00145

Hom.:

Bravo

AF:

0.0152

Asia WGS

AF:

0.00579

AC:

AN:

3470

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 21, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.052

DANN

Benign

0.52

Splicing

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