15-40212643-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_001211.6(BUB1B):c.2530C>T(p.Leu844Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,612,856 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001211.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BUB1B | ENST00000287598.11 | c.2530C>T | p.Leu844Phe | missense_variant | Exon 19 of 23 | 1 | NM_001211.6 | ENSP00000287598.7 | ||
BUB1B | ENST00000412359.7 | c.2572C>T | p.Leu858Phe | missense_variant | Exon 19 of 23 | 2 | ENSP00000398470.3 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152182Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250968Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135690
GnomAD4 exome AF: 0.00000685 AC: 10AN: 1460674Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 726688
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152182Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74340
ClinVar
Submissions by phenotype
Mosaic variegated aneuploidy syndrome 1 Pathogenic:1Uncertain:1
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This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 844 of the BUB1B protein (p.Leu844Phe). This variant is present in population databases (rs28989181, gnomAD 0.004%). This missense change has been observed in individual(s) with mosaic variegated aneuploidy (MVA) and embryonal rhabdomyosarcoma of the soft palate (PMID: 9916837, 15475955, 18548531). ClinVar contains an entry for this variant (Variation ID: 6761). 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 disruptive. Experimental studies have shown that this missense change affects BUB1B function (PMID: 20516114, 25502805). 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. -
Colorectal cancer;C1850343:Mosaic variegated aneuploidy syndrome 1;C1864389:Premature chromatid separation trait Uncertain:1
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Premature chromatid separation trait Other:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at