chr11-111737534-C-G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_181699.3(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. 12/18 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
NM_181699.3 missense

Scores

2
13

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.09
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 id 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.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PPP2R1BNM_181699.3 linkc.1825G>C p.Val609Leu missense_variant Exon 15 of 16 NP_859050.1 P30154-2
PPP2R1BNM_181700.2 linkc.1633G>C p.Val545Leu missense_variant Exon 13 of 14 NP_859051.1 P30154-3
PPP2R1BXM_047427196.1 linkc.1825G>C p.Val609Leu missense_variant Exon 15 of 16 XP_047283152.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PPP2R1BENST00000311129.9 linkc.1825G>C p.Val609Leu missense_variant Exon 15 of 16 1 ENSP00000311344.5 P30154-2
PPP2R1BENST00000426998.6 linkc.1633G>C p.Val545Leu missense_variant Exon 13 of 14 2 ENSP00000410671.2 P30154-3
PPP2R1BENST00000526287.1 linkn.-31G>C upstream_gene_variant 1

Frequencies

GnomAD3 genomes
AF:
0.0284
AC:
4326
AN:
152216
Hom.:
128
Cov.:
33
show subpopulations
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
show subpopulations
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
show subpopulations
Gnomad4 AFR exome
AF:
0.00517
AC:
173
AN:
33480
Gnomad4 AMR exome
AF:
0.0789
AC:
3527
AN:
44718
Gnomad4 ASJ exome
AF:
0.00658
AC:
172
AN:
26136
Gnomad4 EAS exome
AF:
0.000126
AC:
5
AN:
39700
Gnomad4 SAS exome
AF:
0.0427
AC:
3679
AN:
86256
Gnomad4 FIN exome
AF:
0.0214
AC:
1144
AN:
53420
Gnomad4 NFE exome
AF:
0.0383
AC:
42617
AN:
1112008
Gnomad4 Remaining exome
AF:
0.0313
AC:
1893
AN:
60396
Heterozygous variant carriers
0
3034
6068
9102
12136
15170
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Exome Hom
Variant carriers
0
1674
3348
5022
6696
8370
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0284
AC:
4326
AN:
152334
Hom.:
128
Cov.:
33
AF XY:
0.0290
AC XY:
2159
AN XY:
74494
show subpopulations
Gnomad4 AFR
AF:
0.00806
AC:
0.0080556
AN:
0.0080556
Gnomad4 AMR
AF:
0.0805
AC:
0.0804891
AN:
0.0804891
Gnomad4 ASJ
AF:
0.00691
AC:
0.00691244
AN:
0.00691244
Gnomad4 EAS
AF:
0.000771
AC:
0.000771307
AN:
0.000771307
Gnomad4 SAS
AF:
0.0348
AC:
0.034797
AN:
0.034797
Gnomad4 FIN
AF:
0.0246
AC:
0.0245716
AN:
0.0245716
Gnomad4 NFE
AF:
0.0331
AC:
0.0331354
AN:
0.0331354
Gnomad4 OTH
AF:
0.0203
AC:
0.0203214
AN:
0.0203214
Heterozygous variant carriers
0
219
437
656
874
1093
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
46
92
138
184
230
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
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

Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

PPP2R1B-related disorder Benign:1
Nov 18, 2019
PreventionGenetics, part of Exact Sciences
Significance:Benign
Review Status:no assertion criteria provided
Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
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;T
MetaRNN
Benign
0.0020
T;T
MetaSVM
Benign
-1.1
T
PrimateAI
Benign
0.44
T
PROVEAN
Benign
-0.27
N;N
REVEL
Benign
0.052
Sift
Uncertain
0.017
D;D
Sift4G
Benign
0.091
T;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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs45568137; hg19: chr11-111608258; COSMIC: COSV99064490; COSMIC: COSV99064490; API