rs1174693367
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_005188.4(CBL):āc.1694T>Cā(p.Leu565Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,894 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 Uncertain significance (ā ). Synonymous variant affecting the same amino acid position (i.e. L565L) has been classified as Likely benign.
Frequency
Consequence
NM_005188.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CBL | NM_005188.4 | c.1694T>C | p.Leu565Ser | missense_variant | 11/16 | ENST00000264033.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CBL | ENST00000264033.6 | c.1694T>C | p.Leu565Ser | missense_variant | 11/16 | 1 | NM_005188.4 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251452Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135898
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461894Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727248
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
RASopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 19, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CBL protein function. ClinVar contains an entry for this variant (Variation ID: 543973). This variant has not been reported in the literature in individuals affected with CBL-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces leucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 565 of the CBL protein (p.Leu565Ser). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at