Variant 11-119300341-A-AAT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The ENST00000264033.6(CBL):c.*560_*561insAT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 409,830 control chromosomes in the GnomAD database, including 14,217 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4646 hom., cov: 32)

Exomes 𝑓: 0.27 ( 9571 hom. )

Consequence

CBL
ENST00000264033.6 3_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.315

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 11-119300341-A-AAT is Benign according to our data. Variant chr11-119300341-A-AAT is described in ClinVar as [Likely_benign]. Clinvar id is 210589.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CBL	NM_005188.4 linkuse as main transcript	c.560_561insAT		3_prime_UTR_variant	16/16	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.560_561insAT		3_prime_UTR_variant	16/16	1	NM_005188.4	ENSP00000264033	P2

Frequencies

GnomAD3 genomes

AF:

0.243

AC:

36905

AN:

151688

Hom.:

4639

Cov.:

show subpopulations

Gnomad AFR

AF:

0.209

Gnomad AMI

AF:

0.225

Gnomad AMR

AF:

0.200

Gnomad ASJ

AF:

0.333

Gnomad EAS

AF:

0.386

Gnomad SAS

AF:

0.167

Gnomad FIN

AF:

0.272

Gnomad MID

AF:

0.224

Gnomad NFE

AF:

0.260

Gnomad OTH

AF:

0.245

GnomAD4 exome

AF:

0.267

AC:

68901

AN:

258024

Hom.:

9571

Cov.:

AF XY:

0.266

AC XY:

34851

AN XY:

131146

show subpopulations

Gnomad4 AFR exome

AF:

0.211

Gnomad4 AMR exome

AF:

0.183

Gnomad4 ASJ exome

AF:

0.341

Gnomad4 EAS exome

AF:

0.386

Gnomad4 SAS exome

AF:

0.151

Gnomad4 FIN exome

AF:

0.252

Gnomad4 NFE exome

AF:

0.259

Gnomad4 OTH exome

AF:

0.262

GnomAD4 genome

AF:

0.243

AC:

36929

AN:

151806

Hom.:

4646

Cov.:

AF XY:

0.243

AC XY:

18050

AN XY:

74164

show subpopulations

Gnomad4 AFR

AF:

0.209

Gnomad4 AMR

AF:

0.200

Gnomad4 ASJ

AF:

0.333

Gnomad4 EAS

AF:

0.386

Gnomad4 SAS

AF:

0.166

Gnomad4 FIN

AF:

0.272

Gnomad4 NFE

AF:

0.260

Gnomad4 OTH

AF:

0.248

Alfa

AF:

0.253

Hom.:

137

Asia WGS

AF:

0.277

AC:

966

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jul 29, 2015

- -

Noonan syndrome and Noonan-related syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Jan 20, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over