chr15-40220705-A-G
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_001211.6(BUB1B):āc.3099A>Gā(p.Lys1033=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0157 in 1,614,064 control chromosomes in the GnomAD database, including 3,213 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.082 ( 1688 hom., cov: 32)
Exomes š: 0.0088 ( 1525 hom. )
Consequence
BUB1B
NM_001211.6 synonymous
NM_001211.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.91
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]
PAK6 (HGNC:16061): (p21 (RAC1) activated kinase 6) This gene encodes a member of a family of p21-stimulated serine/threonine protein kinases, which contain an amino-terminal Cdc42/Rac interactive binding (CRIB) domain and a carboxyl-terminal kinase domain. These kinases function in a number of cellular processes, including cytoskeleton rearrangement, apoptosis, and the mitogen-activated protein (MAP) kinase signaling pathway. The protein encoded by this gene interacts with androgen receptor (AR) and translocates to the nucleus, where it is involved in transcriptional regulation. Changes in expression of this gene have been linked to prostate cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
Variant 15-40220705-A-G is Benign according to our data. Variant chr15-40220705-A-G is described in ClinVar as [Benign]. Clinvar id is 257638.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=1.91 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BUB1B | NM_001211.6 | c.3099A>G | p.Lys1033= | synonymous_variant | 23/23 | ENST00000287598.11 | |
BUB1B-PAK6 | NM_001128628.3 | c.-201+3038A>G | intron_variant | ||||
LOC107984763 | XR_001751506.2 | n.217+18780T>C | intron_variant, non_coding_transcript_variant | ||||
BUB1B-PAK6 | NM_001128629.3 | c.-118+3038A>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BUB1B | ENST00000287598.11 | c.3099A>G | p.Lys1033= | synonymous_variant | 23/23 | 1 | NM_001211.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0816 AC: 12416AN: 152082Hom.: 1673 Cov.: 32
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GnomAD3 exomes AF: 0.0212 AC: 5342AN: 251486Hom.: 654 AF XY: 0.0160 AC XY: 2177AN XY: 135916
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GnomAD4 exome AF: 0.00885 AC: 12932AN: 1461864Hom.: 1525 Cov.: 31 AF XY: 0.00774 AC XY: 5627AN XY: 727232
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GnomAD4 genome AF: 0.0819 AC: 12468AN: 152200Hom.: 1688 Cov.: 32 AF XY: 0.0795 AC XY: 5915AN XY: 74428
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Colorectal cancer Benign:1
Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 24, 2019 | - - |
Mosaic variegated aneuploidy syndrome 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
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BayesDel_noAF
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DANN
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Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at