rs1893177
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_005188.4(CBL):c.2592C>T(p.Leu864Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00593 in 1,614,182 control chromosomes in the GnomAD database, including 529 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_005188.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CBL | NM_005188.4 | c.2592C>T | p.Leu864Leu | synonymous_variant | Exon 16 of 16 | ENST00000264033.6 | NP_005179.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0310 AC: 4714AN: 152176Hom.: 263 Cov.: 32
GnomAD3 exomes AF: 0.00787 AC: 1979AN: 251462Hom.: 104 AF XY: 0.00575 AC XY: 781AN XY: 135902
GnomAD4 exome AF: 0.00332 AC: 4850AN: 1461888Hom.: 266 Cov.: 31 AF XY: 0.00285 AC XY: 2072AN XY: 727246
GnomAD4 genome AF: 0.0311 AC: 4729AN: 152294Hom.: 263 Cov.: 32 AF XY: 0.0303 AC XY: 2256AN XY: 74476
ClinVar
Submissions by phenotype
not specified Benign:7
p.Leu864Leu in Exon 16 of CBL: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence and has been identified in 10.6% (398/3738) of Af rican American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs1893177). -
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This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
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not provided Benign:2
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CBL-related disorder Benign:1
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. -
Juvenile myelomonocytic leukemia Benign:1
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Cardiovascular phenotype Benign:1
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Noonan syndrome and Noonan-related syndrome Benign:1
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RASopathy Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at