GeneBe

rs750703763

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001211.6(BUB1B):​c.1220T>A​(p.Val407Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. V407G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

BUB1B
NM_001211.6 missense

Scores

12
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.37

Publications

1 publications found
Variant links:
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]
BUB1B Gene-Disease associations (from GenCC):
  • mosaic variegated aneuploidy syndrome 1
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae), G2P
  • rhabdomyosarcoma
    Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
  • mosaic variegated aneuploidy syndrome
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001211.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
BUB1B
NM_001211.6
MANE Select
c.1220T>Ap.Val407Glu
missense
Exon 9 of 23NP_001202.5

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
BUB1B
ENST00000287598.11
TSL:1 MANE Select
c.1220T>Ap.Val407Glu
missense
Exon 9 of 23ENSP00000287598.7O60566-1
BUB1B
ENST00000412359.7
TSL:2
c.1262T>Ap.Val421Glu
missense
Exon 9 of 23ENSP00000398470.3O60566-3
BUB1B
ENST00000918306.1
c.1322T>Ap.Val441Glu
missense
Exon 10 of 24ENSP00000588365.1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

ClinVar submissions as Germline
Significance:Uncertain significance
Revision:criteria provided, single submitter
View on ClinVar
Pathogenic
VUS
Benign
Condition
-
1
-
Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.46
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Uncertain
-0.080
CADD
Uncertain
26
DANN
Uncertain
0.99
DEOGEN2
Benign
0.18
T
Eigen
Uncertain
0.48
Eigen_PC
Uncertain
0.49
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.80
T
M_CAP
Benign
0.017
T
MetaRNN
Uncertain
0.45
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.7
M
PhyloP100
4.4
PrimateAI
Uncertain
0.61
T
PROVEAN
Uncertain
-2.4
N
REVEL
Benign
0.18
Sift
Uncertain
0.011
D
Sift4G
Benign
0.11
T
Polyphen
1.0
D
Vest4
0.52
MutPred
0.30
Gain of ubiquitination at K402 (P = 0.037)
MVP
0.90
MPC
1.0
ClinPred
0.91
D
GERP RS
5.6
Varity_R
0.33
gMVP
0.49
Mutation Taster
=89/11
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs750703763; hg19: chr15-40488907; API