NM_002709.3:c.592+1011C>G

Variant names:

• chr2-28784989-C-G
• rs6725177
• NM_002709.3:c.592+1011C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002709.3(PPP1CB):​c.592+1011C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 143,854 control chromosomes in the GnomAD database, including 14,084 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.42 (14084 hom., cov: 23)
• Consequence: PPP1CB NM_002709.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31
• Publications: 7 publications found

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]

SPDYA (HGNC:30613): (speedy/RINGO cell cycle regulator family member A) Enables protein kinase activator activity and protein kinase binding activity. Involved in several processes, including G1/S transition of mitotic cell cycle; positive regulation of cell population proliferation; and positive regulation of protein kinase activity. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1CB	NM_002709.3	c.592+1011C>G		intron_variant	Intron 5 of 7	ENST00000395366.3	NP_002700.1
PPP1CB	NM_206876.2	c.592+1011C>G		intron_variant	Intron 6 of 8		NP_996759.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1CB	ENST00000395366.3	c.592+1011C>G		intron_variant	Intron 5 of 7	1	NM_002709.3	ENSP00000378769.2

Frequencies

GnomAD3 genomes AF: 0.423 AC: 60859 AN: 143816 Hom.: 14076 Cov.: 23

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.0592

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.436

Gnomad MID AF: 0.526

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.451

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

GnomAD4 genome AF: 0.423 AC: 60856 AN: 143854 Hom.: 14084 Cov.: 23 AF XY: 0.416 AC XY: 28784 AN XY: 69156

African (AFR) AF: 0.304 AC: 11833 AN: 38918

American (AMR) AF: 0.338 AC: 4799 AN: 14182

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 1702 AN: 3424

East Asian (EAS) AF: 0.0592 AC: 299 AN: 5048

South Asian (SAS) AF: 0.435 AC: 2005 AN: 4604

European-Finnish (FIN) AF: 0.436 AC: 3382 AN: 7762

Middle Eastern (MID) AF: 0.521 AC: 146 AN: 280

European-Non Finnish (NFE) AF: 0.531 AC: 35455 AN: 66750

Other (OTH) AF: 0.452 AC: 896 AN: 1984

Alfa AF: 0.312 Hom.: 719

Bravo AF: 0.409

Asia WGS AF: 0.246 AC: 854 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.8
DANN	Benign	0.57
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6725177; hg19: chr2-29007855;