11-119206392-G-C
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_005188.4(CBL):c.-26G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000299 in 1,499,678 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0016 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00015 ( 0 hom. )
Consequence
CBL
NM_005188.4 5_prime_UTR
NM_005188.4 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.813
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 -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BP6
Variant 11-119206392-G-C is Benign according to our data. Variant chr11-119206392-G-C is described in ClinVar as [Benign]. Clinvar id is 1262370.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0016 (243/152072) while in subpopulation AFR AF= 0.00554 (230/41534). AF 95% confidence interval is 0.00495. There are 1 homozygotes in gnomad4. There are 134 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 243 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CBL | NM_005188.4 | c.-26G>C | 5_prime_UTR_variant | 1/16 | ENST00000264033.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CBL | ENST00000264033.6 | c.-26G>C | 5_prime_UTR_variant | 1/16 | 1 | NM_005188.4 | P2 |
Frequencies
GnomAD3 genomes AF: 0.00160 AC: 243AN: 151958Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000325 AC: 38AN: 117010Hom.: 0 AF XY: 0.000355 AC XY: 23AN XY: 64716
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GnomAD4 exome AF: 0.000152 AC: 205AN: 1347606Hom.: 0 Cov.: 31 AF XY: 0.000125 AC XY: 83AN XY: 662986
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GnomAD4 genome AF: 0.00160 AC: 243AN: 152072Hom.: 1 Cov.: 32 AF XY: 0.00180 AC XY: 134AN XY: 74340
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at