Variant 11-119206440-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005188.4(CBL):c.23G>C(p.Ser8Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,424,922 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CBL
NM_005188.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.33

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]

CBL links:

Genome browser will be placed here

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=0.16483742).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CBL	NM_005188.4 linkuse as main transcript	c.23G>C	p.Ser8Thr	missense_variant	1/16	ENST00000264033.6	NP_005179.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CBL	ENST00000264033.6 linkuse as main transcript	c.23G>C	p.Ser8Thr	missense_variant	1/16	1	NM_005188.4	ENSP00000264033.3		P22681

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000523

AC:

AN:

191226

Hom.:

AF XY:

0.00000957

AC XY:

AN XY:

104510

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000383

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000140

AC:

AN:

1424922

Hom.:

Cov.:

AF XY:

0.00000283

AC XY:

AN XY:

706154

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000243

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.062

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.32

T;.;T;.

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.68

T;T;T;T

M_CAP

Pathogenic

0.72

MetaRNN

Benign

0.16

T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.0

N;.;.;.

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.21

N;.;.;.

REVEL

Benign

0.16

Sift

Benign

0.14

T;.;.;.

Sift4G

Benign

0.26

T;T;T;.

Polyphen

0.15

B;.;.;.

Vest4

0.16

MutPred

0.11

Loss of ubiquitination at K7 (P = 0.1016);Loss of ubiquitination at K7 (P = 0.1016);Loss of ubiquitination at K7 (P = 0.1016);.;

MVP

0.81

MPC

0.83

ClinPred

0.28

GERP RS

2.4

Varity_R

0.17

gMVP

0.21

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over