rs28989189
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001211.6(BUB1B):āc.348T>Cā(p.Tyr116Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00932 in 1,613,708 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0060 ( 4 hom., cov: 32)
Exomes š: 0.0097 ( 110 hom. )
Consequence
BUB1B
NM_001211.6 synonymous
NM_001211.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.162
Genes affected
BUB1B (HGNC:1149): (BUB1 mitotic checkpoint serine/threonine kinase B) This gene encodes a kinase involved in spindle checkpoint function. The protein has been localized to the kinetochore and plays a role in the inhibition of the anaphase-promoting complex/cyclosome (APC/C), delaying the onset of anaphase and ensuring proper chromosome segregation. Impaired spindle checkpoint function has been found in many forms of cancer. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
Variant 15-40170645-T-C is Benign according to our data. Variant chr15-40170645-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 238666.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-40170645-T-C is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=0.162 with no splicing effect.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00603 (918/152326) while in subpopulation NFE AF= 0.00966 (657/68030). AF 95% confidence interval is 0.00905. There are 4 homozygotes in gnomad4. There are 422 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 4 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BUB1B | NM_001211.6 | c.348T>C | p.Tyr116Tyr | synonymous_variant | 4/23 | ENST00000287598.11 | NP_001202.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BUB1B | ENST00000287598.11 | c.348T>C | p.Tyr116Tyr | synonymous_variant | 4/23 | 1 | NM_001211.6 | ENSP00000287598.7 | ||
BUB1B | ENST00000412359.7 | c.390T>C | p.Tyr130Tyr | synonymous_variant | 4/23 | 2 | ENSP00000398470.3 |
Frequencies
GnomAD3 genomes AF: 0.00602 AC: 917AN: 152208Hom.: 4 Cov.: 32
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GnomAD3 exomes AF: 0.00694 AC: 1745AN: 251348Hom.: 14 AF XY: 0.00727 AC XY: 987AN XY: 135852
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GnomAD4 exome AF: 0.00967 AC: 14127AN: 1461382Hom.: 110 Cov.: 32 AF XY: 0.00961 AC XY: 6984AN XY: 727022
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GnomAD4 genome AF: 0.00603 AC: 918AN: 152326Hom.: 4 Cov.: 32 AF XY: 0.00566 AC XY: 422AN XY: 74496
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 14, 2020 | This variant is associated with the following publications: (PMID: 16182441) - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2024 | BUB1B: BP4, BP7, BS1, BS2 - |
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 05, 2017 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 12, 2022 | This alteration is classified as likely 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. - |
Colorectal cancer Benign:1
Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Mosaic variegated aneuploidy syndrome 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 30, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
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