2-28802613-A-G

Variant names:

• chr2-28802613-A-G
• rs3190
• NM_002709.3:c.*3310A>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.*3310A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 152,096 control chromosomes in the GnomAD database, including 20,288 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 0.51 (20288 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: PPP1CB NM_002709.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48
• Publications: 23 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002709.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1CB	NM_002709.3	MANE Select	c.*3310A>G		3_prime_UTR	Exon 8 of 8	NP_002700.1
	PPP1CB	NM_206876.2		c.*3310A>G		3_prime_UTR	Exon 9 of 9	NP_996759.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1CB	ENST00000395366.3	TSL:1 MANE Select	c.*3310A>G		3_prime_UTR	Exon 8 of 8	ENSP00000378769.2
	PPP1CB	ENST00000455580.6	TSL:3	c.*3310A>G		3_prime_UTR	Exon 8 of 8	ENSP00000390715.2
	SPDYA	ENST00000462832.5	TSL:2	n.807+3314A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77182 AN: 151978 Hom.: 20277 Cov.: 32

Gnomad AFR AF: 0.425

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.533

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.508 AC: 77220 AN: 152096 Hom.: 20288 Cov.: 32 AF XY: 0.508 AC XY: 37800 AN XY: 74364

African (AFR) AF: 0.425 AC: 17612 AN: 41484

American (AMR) AF: 0.450 AC: 6878 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.524 AC: 1819 AN: 3472

East Asian (EAS) AF: 0.231 AC: 1198 AN: 5182

South Asian (SAS) AF: 0.534 AC: 2578 AN: 4824

European-Finnish (FIN) AF: 0.580 AC: 6132 AN: 10568

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.578 AC: 39261 AN: 67980

Other (OTH) AF: 0.535 AC: 1128 AN: 2110

Alfa AF: 0.550 Hom.: 50509

Bravo AF: 0.489

Asia WGS AF: 0.408 AC: 1422 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.021
DANN	Benign	0.40
PhyloP100		-1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs3190; hg19: chr2-29025479;