chr2-28751472-C-G

Variant names:

• chr2-28751472-C-G
• rs115890199
• ENST00000653462.1:n.251G>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The ENST00000653462.1(PPP1CB-DT):​n.251G>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 0.00416 in 152,364 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0042 (6 hom., cov: 34)
• Consequence: PPP1CB-DT ENST00000653462.1 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.705
• Publications: 0 publications found

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]

PPP1CB Gene-Disease associations (from GenCC):

• Noonan syndrome-like disorder with loose anagen hair

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Noonan syndrome-like disorder with loose anagen hair 2

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae)
• cardiofaciocutaneous syndrome

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• Costello syndrome

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• Noonan syndrome

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• Noonan syndrome with multiple lentigines

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 2-28751472-C-G is Benign according to our data. Variant chr2-28751472-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1217960.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 6 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000653462.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1CB	NM_206876.2		c.-436C>G		upstream_gene	N/A	NP_996759.1	P62140

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1CB-DT	ENST00000653462.1		n.251G>C		non_coding_transcript_exon	Exon 1 of 4
	PPP1CB-DT	ENST00000658445.1		n.119G>C		non_coding_transcript_exon	Exon 1 of 5
	PPP1CB-DT	ENST00000665023.2		n.203G>C		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes AF: 0.00416 AC: 634 AN: 152246 Hom.: 6 Cov.: 34

Gnomad AFR AF: 0.0145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00287

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00416 AC: 634 AN: 152364 Hom.: 6 Cov.: 34 AF XY: 0.00393 AC XY: 293 AN XY: 74506

African (AFR) AF: 0.0144 AC: 600 AN: 41586

American (AMR) AF: 0.00131 AC: 20 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68038

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00277 Hom.: 0

Bravo AF: 0.00450

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.6
DANN	Benign	0.60
PhyloP100		-0.70
PromoterAI		-0.064	Neutral

Splicing

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

Other links and lift over

dbSNP: rs115890199; hg19: chr2-28974338;