2-28751725-C-G

Position:

• chr2-28751725-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The XR_007086259.1(PPP1CB-DT):​n.32G>C 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 0.0192 in 244,620 control chromosomes in the GnomAD database, including 184 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.029 (179 hom., cov: 31)
  • Exomes 𝑓: 0.0031 (5 hom.)
• Consequence: PPP1CB-DT XR_007086259.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.07

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 2-28751725-C-G is Benign according to our data. Variant chr2-28751725-C-G is described in ClinVar as [Benign]. Clinvar id is 1222948.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.086 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP1CB-DT	XR_007086259.1	n.32G>C		non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP1CB	ENST00000420282.6	c.-146C>G		5_prime_UTR_variant	1/9	4		P1
PPP1CB	ENST00000455580.6	c.-128C>G		5_prime_UTR_variant	1/8	3
PPP1CB	ENST00000441461.6			upstream_gene_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.0289 AC: 4387 AN: 151984 Hom.: 177 Cov.: 31

Gnomad AFR AF: 0.0881

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0261

Gnomad ASJ AF: 0.0205

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000378

Gnomad MID AF: 0.0478

Gnomad NFE AF: 0.00271

Gnomad OTH AF: 0.0325

GnomAD4 exome AF: 0.00307 AC: 284 AN: 92528 Hom.: 5 Cov.: 0 AF XY: 0.00264 AC XY: 142 AN XY: 53756

Gnomad4 AFR exome AF: 0.0659

Gnomad4 AMR exome AF: 0.0109

Gnomad4 ASJ exome AF: 0.0211

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000243

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00214

Gnomad4 OTH exome AF: 0.00917

GnomAD4 genome AF: 0.0290 AC: 4406 AN: 152092 Hom.: 179 Cov.: 31 AF XY: 0.0288 AC XY: 2145 AN XY: 74358

Gnomad4 AFR AF: 0.0884

Gnomad4 AMR AF: 0.0260

Gnomad4 ASJ AF: 0.0205

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000378

Gnomad4 NFE AF: 0.00268

Gnomad4 OTH AF: 0.0322

Alfa AF: 0.0223 Hom.: 15

Bravo AF: 0.0334

Asia WGS AF: 0.00493 AC: 17 AN: 3460

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	2.3
DANN	Benign	0.85

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs115360250; hg19: chr2-28974591;