Variant rs1047417 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005188.4(CBL):c.*2045A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 233,018 control chromosomes in the GnomAD database, including 7,625 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4518 hom., cov: 32)

Exomes 𝑓: 0.27 ( 3107 hom. )

Consequence

CBL
NM_005188.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.340

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 11-119301826-A-G is Benign according to our data. Variant chr11-119301826-A-G is described in ClinVar as [Benign]. Clinvar id is 302818.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.329 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.*2045A>G		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.*2045A>G		3_prime_UTR_variant	16/16	1	NM_005188.4	ENSP00000264033.3		P22681

Frequencies

GnomAD3 genomes

AF:

0.239

AC:

36286

AN:

151964

Hom.:

4512

Cov.:

show subpopulations

Gnomad AFR

AF:

0.209

Gnomad AMI

AF:

0.228

Gnomad AMR

AF:

0.200

Gnomad ASJ

AF:

0.333

Gnomad EAS

AF:

0.342

Gnomad SAS

AF:

0.166

Gnomad FIN

AF:

0.258

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.255

Gnomad OTH

AF:

0.242

GnomAD4 exome

AF:

0.274

AC:

22155

AN:

80936

Hom.:

3107

Cov.:

AF XY:

0.273

AC XY:

10148

AN XY:

37198

show subpopulations

Gnomad4 AFR exome

AF:

0.221

Gnomad4 AMR exome

AF:

0.206

Gnomad4 ASJ exome

AF:

0.337

Gnomad4 EAS exome

AF:

0.358

Gnomad4 SAS exome

AF:

0.154

Gnomad4 FIN exome

AF:

0.267

Gnomad4 NFE exome

AF:

0.259

Gnomad4 OTH exome

AF:

0.260

GnomAD4 genome

AF:

0.239

AC:

36307

AN:

152082

Hom.:

4518

Cov.:

AF XY:

0.238

AC XY:

17716

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.209

Gnomad4 AMR

AF:

0.200

Gnomad4 ASJ

AF:

0.333

Gnomad4 EAS

AF:

0.342

Gnomad4 SAS

AF:

0.165

Gnomad4 FIN

AF:

0.258

Gnomad4 NFE

AF:

0.256

Gnomad4 OTH

AF:

0.244

Alfa

AF:

0.256

Hom.:

10431

Bravo

AF:

0.236

Asia WGS

AF:

0.267

AC:

933

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

CBL-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.53

DANN

Benign

0.23

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.

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