2-28751600-T-C

Position:

• chr2-28751600-T-C

Variant summary

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

The ENST00000666397.1(PPP1CB-DT):​n.1A>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 0.666 in 161,858 control chromosomes in the GnomAD database, including 36,281 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.67 (34223 hom., cov: 36)
  • Exomes 𝑓: 0.64 (2058 hom.)
• Consequence: PPP1CB-DT ENST00000666397.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.14

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=-0.8).
• BP6: Variant 2-28751600-T-C is Benign according to our data. Variant chr2-28751600-T-C is described in ClinVar as [Benign]. Clinvar id is 1261656.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.716 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP1CB-DT	XR_007086259.1	n.114+43A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP1CB-DT	ENST00000666397.1	n.1A>G		non_coding_transcript_exon_variant	1/4

Frequencies

GnomAD3 genomes AF: 0.668 AC: 101622 AN: 152120 Hom.: 34203 Cov.: 36

Gnomad AFR AF: 0.602

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.685

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.722

Gnomad SAS AF: 0.736

Gnomad FIN AF: 0.705

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.697

GnomAD4 exome AF: 0.643 AC: 6188 AN: 9620 Hom.: 2058 Cov.: 0 AF XY: 0.640 AC XY: 3328 AN XY: 5204

Gnomad4 AFR exome AF: 0.620

Gnomad4 AMR exome AF: 0.650

Gnomad4 ASJ exome AF: 0.516

Gnomad4 EAS exome AF: 0.618

Gnomad4 SAS exome AF: 0.669

Gnomad4 FIN exome AF: 0.639

Gnomad4 NFE exome AF: 0.638

Gnomad4 OTH exome AF: 0.662

GnomAD4 genome AF: 0.668 AC: 101686 AN: 152238 Hom.: 34223 Cov.: 36 AF XY: 0.671 AC XY: 49954 AN XY: 74424

Gnomad4 AFR AF: 0.602

Gnomad4 AMR AF: 0.685

Gnomad4 ASJ AF: 0.653

Gnomad4 EAS AF: 0.722

Gnomad4 SAS AF: 0.736

Gnomad4 FIN AF: 0.705

Gnomad4 NFE AF: 0.692

Gnomad4 OTH AF: 0.700

Alfa AF: 0.674 Hom.: 4317

Bravo AF: 0.663

Asia WGS AF: 0.745 AC: 2591 AN: 3478

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	clinical testing	GeneDx	Oct 01, 2018	- -
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	-0.80
CADD	Benign	8.1
DANN	Benign	0.43

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7598876; hg19: chr2-28974466;