15-40161230-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS1

The NM_001211.6(BUB1B):​c.10G>A​(p.Val4Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00031 in 1,613,460 control chromosomes in the GnomAD database, including 1 homozygotes. 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00016 ( 1 hom. )

Consequence

BUB1B
NM_001211.6 missense

Scores

19

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:5O:1

Conservation

PhyloP100: -0.408
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0028975308).
BP6
Variant 15-40161230-G-A is Benign according to our data. Variant chr15-40161230-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 133764.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00173 (264/152312) while in subpopulation AFR AF= 0.00628 (261/41558). AF 95% confidence interval is 0.00565. There are 0 homozygotes in gnomad4. There are 109 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BUB1BNM_001211.6 linkc.10G>A p.Val4Met missense_variant Exon 1 of 23 ENST00000287598.11 NP_001202.5 O60566-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BUB1BENST00000287598.11 linkc.10G>A p.Val4Met missense_variant Exon 1 of 23 1 NM_001211.6 ENSP00000287598.7 O60566-1
BUB1BENST00000412359.7 linkc.10G>A p.Val4Met missense_variant Exon 1 of 23 2 ENSP00000398470.3 O60566-3

Frequencies

GnomAD3 genomes
AF:
0.00172
AC:
262
AN:
152194
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00625
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000958
GnomAD3 exomes
AF:
0.000404
AC:
100
AN:
247566
Hom.:
0
AF XY:
0.000276
AC XY:
37
AN XY:
134192
show subpopulations
Gnomad AFR exome
AF:
0.00604
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000179
Gnomad OTH exome
AF:
0.000332
GnomAD4 exome
AF:
0.000162
AC:
236
AN:
1461148
Hom.:
1
Cov.:
31
AF XY:
0.000120
AC XY:
87
AN XY:
726792
show subpopulations
Gnomad4 AFR exome
AF:
0.00624
Gnomad4 AMR exome
AF:
0.0000896
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.000331
GnomAD4 genome
AF:
0.00173
AC:
264
AN:
152312
Hom.:
0
Cov.:
32
AF XY:
0.00146
AC XY:
109
AN XY:
74484
show subpopulations
Gnomad4 AFR
AF:
0.00628
Gnomad4 AMR
AF:
0.0000653
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000948
Alfa
AF:
0.000709
Hom.:
0
Bravo
AF:
0.00202
ESP6500AA
AF:
0.00477
AC:
21
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000453
AC:
55

ClinVar

Significance: Likely benign
Submissions summary: Benign:5Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1Other:1
Sep 19, 2013
ITMI
Significance: not provided
Review Status: no classification provided
Collection Method: reference population

- -

Mar 12, 2018
Eurofins Ntd Llc (ga)
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Inborn genetic diseases Benign:1
Aug 27, 2021
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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. -

BUB1B-related disorder Benign:1
Apr 14, 2021
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Mosaic variegated aneuploidy syndrome 1 Benign:1
Dec 18, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.083
BayesDel_addAF
Benign
-0.73
T
BayesDel_noAF
Benign
-0.82
CADD
Benign
9.1
DANN
Benign
0.69
DEOGEN2
Benign
0.077
T;.
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.0025
N
LIST_S2
Benign
0.59
T;T
M_CAP
Benign
0.0023
T
MetaRNN
Benign
0.0029
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-1.4
N;N
PrimateAI
Benign
0.27
T
PROVEAN
Benign
-0.28
N;N
REVEL
Benign
0.076
Sift
Benign
0.33
T;T
Sift4G
Benign
0.50
T;T
Polyphen
0.0
B;.
Vest4
0.027
MVP
0.59
MPC
0.20
ClinPred
0.0089
T
GERP RS
-5.2
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.0
Varity_R
0.048
gMVP
0.13

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs147549987; hg19: chr15-40453431; API