chr2-28751664-A-C

Position:

• chr2-28751664-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.84

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=-0.81).
• 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	UniProt
PPP1CB-DT	XR_007086259.1	n.93T>G		non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP1CB	ENST00000455580.6	c.-189A>C		5_prime_UTR_variant	1/8	3
PPP1CB-DT	ENST00000653462.1	n.59T>G		non_coding_transcript_exon_variant	1/4
PPP1CB	ENST00000420282.6			upstream_gene_variant		4		P1
PPP1CB-DT	ENST00000665023.1			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.0143 AC: 2171 AN: 152194 Hom.: 47 Cov.: 31

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: 98 AN: 31836 Hom.: 0 Cov.: 0 AF XY: 0.00223 AC XY: 40 AN XY: 17920

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.: 47 Cov.: 31 AF XY: 0.0147 AC XY: 1098 AN XY: 74476

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.: 0

Bravo AF: 0.0152

Asia WGS AF: 0.00579 AC: 20 AN: 3470

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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

Other links and lift over

dbSNP: rs147139861; hg19: chr2-28974530;