chr11-119206322-G-A
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The ENST00000634586.1(CBL):c.-96G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00192 in 1,034,480 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0084 ( 24 hom., cov: 32)
Exomes 𝑓: 0.00081 ( 15 hom. )
Consequence
CBL
ENST00000634586.1 5_prime_UTR
ENST00000634586.1 5_prime_UTR
Scores
1
1
Clinical Significance
Conservation
PhyloP100: -0.663
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 Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
Variant 11-119206322-G-A is Benign according to our data. Variant chr11-119206322-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 302772.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00838 (1273/151932) while in subpopulation AFR AF= 0.0293 (1215/41482). AF 95% confidence interval is 0.0279. There are 24 homozygotes in gnomad4. There are 603 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 1273 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CBL | NM_005188.4 | upstream_gene_variant | ENST00000264033.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CBL | ENST00000634586.1 | c.-96G>A | 5_prime_UTR_variant | 1/18 | 5 | ||||
CBL | ENST00000634840.1 | c.-96G>A | 5_prime_UTR_variant | 1/15 | 5 | A2 | |||
CBL | ENST00000264033.6 | upstream_gene_variant | 1 | NM_005188.4 | P2 | ||||
CBL | ENST00000700472.1 | upstream_gene_variant |
Frequencies
GnomAD3 genomes AF: 0.00835 AC: 1267AN: 151824Hom.: 23 Cov.: 32
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GnomAD4 exome AF: 0.000809 AC: 714AN: 882548Hom.: 15 Cov.: 12 AF XY: 0.000687 AC XY: 302AN XY: 439484
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GnomAD4 genome AF: 0.00838 AC: 1273AN: 151932Hom.: 24 Cov.: 32 AF XY: 0.00812 AC XY: 603AN XY: 74266
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ClinVar
Significance: Benign/Likely 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
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 15, 2019 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at