rs1188095865

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000264033.6(CBL):​c.1296T>A​(p.Asp432Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D432D) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

CBL
ENST00000264033.6 missense

Scores

3
8
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.304
Variant links:
Genes affected
CBL (HGNC:1541): (Cbl proto-oncogene) This gene is a proto-oncogene that encodes a RING finger E3 ubiquitin ligase. The encoded protein is one of the enzymes required for targeting substrates for degradation by the proteasome. This protein mediates the transfer of ubiquitin from ubiquitin conjugating enzymes (E2) to specific substrates. This protein also contains an N-terminal phosphotyrosine binding domain that allows it to interact with numerous tyrosine-phosphorylated substrates and target them for proteasome degradation. As such it functions as a negative regulator of many signal transduction pathways. This gene has been found to be mutated or translocated in many cancers including acute myeloid leukaemia, and expansion of CGG repeats in the 5' UTR has been associated with Jacobsen syndrome. Mutations in this gene are also the cause of Noonan syndrome-like disorder. [provided by RefSeq, Jul 2016]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.24852544).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CBLNM_005188.4 linkuse as main transcriptc.1296T>A p.Asp432Glu missense_variant 9/16 ENST00000264033.6 NP_005179.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CBLENST00000264033.6 linkuse as main transcriptc.1296T>A p.Asp432Glu missense_variant 9/161 NM_005188.4 ENSP00000264033 P2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.97
BayesDel_addAF
Uncertain
0.082
D
BayesDel_noAF
Benign
-0.12
CADD
Benign
21
DANN
Benign
0.94
DEOGEN2
Pathogenic
0.83
D;.;T;.
Eigen
Benign
-0.14
Eigen_PC
Benign
-0.026
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Uncertain
0.93
D;D;D;D
M_CAP
Uncertain
0.11
D
MetaRNN
Benign
0.25
T;T;T;T
MetaSVM
Uncertain
0.30
D
MutationAssessor
Uncertain
2.0
M;.;.;.
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.86
D
PROVEAN
Uncertain
-2.9
D;.;.;.
REVEL
Uncertain
0.40
Sift
Benign
0.081
T;.;.;.
Sift4G
Benign
0.067
T;T;T;.
Polyphen
0.073
B;.;.;.
Vest4
0.60
MutPred
0.30
Gain of disorder (P = 0.1258);Gain of disorder (P = 0.1258);Gain of disorder (P = 0.1258);.;
MVP
0.97
MPC
0.19
ClinPred
0.42
T
GERP RS
3.7
Varity_R
0.56
gMVP
0.30

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-119149288; API