2-28751800-G-A

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.-108G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000355 in 441,740 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00048 (1 hom.)
• Consequence: PPP1CB NM_206876.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.19

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:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.2).
• BP6: Variant 2-28751800-G-A is Benign according to our data. Variant chr2-28751800-G-A is described in ClinVar as [Benign]. Clinvar id is 1265254.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 19 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP1CB	NM_206876.2	c.-108G>A		5_prime_UTR_variant	1/9
PPP1CB	NM_002709.3			upstream_gene_variant		ENST00000395366.3
PPP1CB-DT	XR_007086259.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP1CB	ENST00000395366.3			upstream_gene_variant		1	NM_002709.3	P1

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 19 AN: 152204 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000289

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000368 AC: 22 AN: 59804 Hom.: 0 AF XY: 0.000418 AC XY: 14 AN XY: 33512

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000907

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00194

Gnomad FIN exome AF: 0.000534

Gnomad NFE exome AF: 0.0000310

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000477 AC: 138 AN: 289428 Hom.: 1 Cov.: 0 AF XY: 0.000718 AC XY: 114 AN XY: 158666

Gnomad4 AFR exome AF: 0.000346

Gnomad4 AMR exome AF: 0.000628

Gnomad4 ASJ exome AF: 0.000129

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00263

Gnomad4 FIN exome AF: 0.0000625

Gnomad4 NFE exome AF: 0.0000519

Gnomad4 OTH exome AF: 0.0000640

GnomAD4 genome AF: 0.000125 AC: 19 AN: 152312 Hom.: 0 Cov.: 30 AF XY: 0.000148 AC XY: 11 AN XY: 74486

Gnomad4 AFR AF: 0.000289

Gnomad4 AMR AF: 0.0000653

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000828

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00

Bravo AF: 0.000136

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

Aug 04, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.20
Cadd	Benign	22
Dann	Uncertain	0.99

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: rs766627964; hg19: chr2-28974666;