ENST00000311129.9:c.1825G>C

Variant names:

• chr11-111737534-C-G
• rs45568137
• ENST00000311129.9:c.1825G>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The ENST00000311129.9(PPP2R1B):​c.1825G>C​(p.Val609Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0357 in 1,614,216 control chromosomes in the GnomAD database, including 1,326 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.028 (128 hom., cov: 33)
  • Exomes 𝑓: 0.037 (1198 hom.)
• Consequence: PPP2R1B ENST00000311129.9 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.09
• Publications: 12 publications found

Genes affected

PPP2R1B (HGNC:9303): (protein phosphatase 2 scaffold subunit Abeta) This gene encodes a constant regulatory subunit of protein phosphatase 2. Protein phosphatase 2 is one of the four major Ser/Thr phosphatases, and it is implicated in the negative control of cell growth and division. It consists of a common heteromeric core enzyme, which is composed of a catalytic subunit and a constant regulatory subunit, that associates with a variety of regulatory subunits. The constant regulatory subunit A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit. This gene encodes a beta isoform of the constant regulatory subunit A. Mutations in this gene have been associated with some lung and colon cancers. Alternatively spliced transcript variants have been described. [provided by RefSeq, Apr 2010]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0020316243).
• BP6: Variant 11-111737534-C-G is Benign according to our data. Variant chr11-111737534-C-G is described in ClinVar as Benign. ClinVar VariationId is 3057072.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0768 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000311129.9. 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
	PPP2R1B	NM_181699.3		c.1825G>C	p.Val609Leu	missense	Exon 15 of 16	NP_859050.1	P30154-2
	PPP2R1B	NM_181700.2		c.1633G>C	p.Val545Leu	missense	Exon 13 of 14	NP_859051.1	P30154-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2R1B	ENST00000311129.9	TSL:1	c.1825G>C	p.Val609Leu	missense	Exon 15 of 16	ENSP00000311344.5	P30154-2
	PPP2R1B	ENST00000426998.6	TSL:2	c.1633G>C	p.Val545Leu	missense	Exon 13 of 14	ENSP00000410671.2	P30154-3
	PPP2R1B	ENST00000526287.1	TSL:1	n.-31G>C		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.0284 AC: 4326 AN: 152216 Hom.: 128 Cov.: 33

Gnomad AFR AF: 0.00808

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0806

Gnomad ASJ AF: 0.00691

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0344

Gnomad FIN AF: 0.0246

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0331

Gnomad OTH AF: 0.0205

GnomAD2 exomes AF: 0.0343 AC: 8621 AN: 251466 AF XY: 0.0343

Gnomad AFR exome AF: 0.00738

Gnomad AMR exome AF: 0.0809

Gnomad ASJ exome AF: 0.00744

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0248

Gnomad NFE exome AF: 0.0322

Gnomad OTH exome AF: 0.0367

GnomAD4 exome AF: 0.0365 AC: 53372 AN: 1461882 Hom.: 1198 Cov.: 31 AF XY: 0.0367 AC XY: 26673 AN XY: 727244

African (AFR) AF: 0.00517 AC: 173 AN: 33480

American (AMR) AF: 0.0789 AC: 3527 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00658 AC: 172 AN: 26136

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39700

South Asian (SAS) AF: 0.0427 AC: 3679 AN: 86256

European-Finnish (FIN) AF: 0.0214 AC: 1144 AN: 53420

Middle Eastern (MID) AF: 0.0281 AC: 162 AN: 5768

European-Non Finnish (NFE) AF: 0.0383 AC: 42617 AN: 1112008

Other (OTH) AF: 0.0313 AC: 1893 AN: 60396

GnomAD4 genome AF: 0.0284 AC: 4326 AN: 152334 Hom.: 128 Cov.: 33 AF XY: 0.0290 AC XY: 2159 AN XY: 74494

African (AFR) AF: 0.00806 AC: 335 AN: 41586

American (AMR) AF: 0.0805 AC: 1231 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00691 AC: 24 AN: 3472

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5186

South Asian (SAS) AF: 0.0348 AC: 168 AN: 4828

European-Finnish (FIN) AF: 0.0246 AC: 261 AN: 10622

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0331 AC: 2254 AN: 68024

Other (OTH) AF: 0.0203 AC: 43 AN: 2116

Alfa AF: 0.0304 Hom.: 68

Bravo AF: 0.0300

TwinsUK AF: 0.0429 AC: 159

ALSPAC AF: 0.0439 AC: 169

ESP6500AA AF: 0.0129 AC: 57

ESP6500EA AF: 0.0350 AC: 301

ExAC AF: 0.0314 AC: 3818

Asia WGS AF: 0.0150 AC: 52 AN: 3478

EpiCase AF: 0.0328

EpiControl AF: 0.0338

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	PPP2R1B-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	21
DANN	Uncertain	0.99
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.76	T
MetaRNN	Benign	0.0020	T
MetaSVM	Benign	-1.1	T
PhyloP100		1.1
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.27	N
REVEL	Benign	0.052
Sift	Uncertain	0.017	D
Sift4G	Benign	0.091	T
Polyphen		0.0	B
Vest4		0.064
MutPred		0.23		Loss of methylation at K610 (P = 0.0725)
MPC		0.23
ClinPred		0.021	T
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.14
Mutation Taster		=95/5	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs45568137; hg19: chr11-111608258; COSMIC: COSV99064490; COSMIC: COSV99064490;