rs146795655
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBS1_Supporting
The NM_001211.6(BUB1B):c.1478C>T(p.Thr493Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000164 in 1,613,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T493S) has been classified as Uncertain significance.
Frequency
Consequence
NM_001211.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BUB1B | NM_001211.6 | c.1478C>T | p.Thr493Ile | missense_variant | 11/23 | ENST00000287598.11 | |
LOC107984763 | XR_001751506.2 | n.218-20119G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BUB1B | ENST00000287598.11 | c.1478C>T | p.Thr493Ile | missense_variant | 11/23 | 1 | NM_001211.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000125 AC: 19AN: 152188Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000135 AC: 34AN: 251274Hom.: 0 AF XY: 0.000125 AC XY: 17AN XY: 135814
GnomAD4 exome AF: 0.000168 AC: 245AN: 1461636Hom.: 0 Cov.: 31 AF XY: 0.000169 AC XY: 123AN XY: 727114
GnomAD4 genome ? AF: 0.000125 AC: 19AN: 152306Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8AN XY: 74476
ClinVar
Submissions by phenotype
Carcinoma of colon;C1850343:Mosaic variegated aneuploidy syndrome 1;C1864389:Premature chromatid separation trait Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 20, 2019 | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 27331020, 24728327) - |
Mosaic variegated aneuploidy syndrome 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 30, 2023 | This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 493 of the BUB1B protein (p.Thr493Ile). This variant is present in population databases (rs146795655, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with BUB1B-related conditions. ClinVar contains an entry for this variant (Variation ID: 133767). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. - |
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at