rs727502913
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_005188.4(CBL):c.801C>G(p.Gly267=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,613,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000017 ( 0 hom. )
Consequence
CBL
NM_005188.4 synonymous
NM_005188.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.16
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 -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
?
Variant 11-119274885-C-G is Benign according to our data. Variant chr11-119274885-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 162830.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-1.16 with no splicing effect.
BS2
?
High AC in GnomAdExome at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CBL | NM_005188.4 | c.801C>G | p.Gly267= | synonymous_variant | 5/16 | ENST00000264033.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CBL | ENST00000264033.6 | c.801C>G | p.Gly267= | synonymous_variant | 5/16 | 1 | NM_005188.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152150Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251476Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135912
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GnomAD4 exome AF: 0.0000171 AC: 25AN: 1461654Hom.: 0 Cov.: 33 AF XY: 0.0000124 AC XY: 9AN XY: 727136
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152150Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74324
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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 | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 20, 2014 | Gly267Gly in exon 5 of CBL: This variant is not expected to have clinical signif icance because it does not alter an amino acid residue and is not located within the splice consensus sequence. - |
RASopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 23, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
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Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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