rs147549987

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 16/22 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

Clinical Significance

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

Conservation

PhyloP100: -0.408

Publications

2 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: ClinGen, Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae)
rhabdomyosarcoma
Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
mosaic variegated aneuploidy syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

BUB1B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BUB1B	NM_001211.6	MANE Select	c.10G>A	p.Val4Met	missense	Exon 1 of 23	NP_001202.5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BUB1B	ENST00000287598.11	TSL:1 MANE Select	c.10G>A	p.Val4Met	missense	Exon 1 of 23	ENSP00000287598.7	O60566-1
BUB1B	ENST00000412359.7	TSL:2	c.10G>A	p.Val4Met	missense	Exon 1 of 23	ENSP00000398470.3	O60566-3
BUB1B	ENST00000918306.1		c.10G>A	p.Val4Met	missense	Exon 1 of 24	ENSP00000588365.1

Frequencies

GnomAD3 genomes

AF:

0.00172

AC:

262

AN:

152194

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.000404

AC:

100

AN:

247566

AF XY:

0.000276

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 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.:

Cov.:

AF XY:

0.000120

AC XY:

AN XY:

726792

show subpopulations

African (AFR)

AF:

0.00624

AC:

209

AN:

33468

American (AMR)

AF:

0.0000896

AC:

AN:

44628

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39678

South Asian (SAS)

AF:

0.00

AC:

AN:

86068

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53372

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1111680

Other (OTH)

AF:

0.000331

AC:

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00173

AC:

264

AN:

152312

Hom.:

Cov.:

AF XY:

0.00146

AC XY:

109

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.00628

AC:

261

AN:

41558

American (AMR)

AF:

0.0000653

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68022

Other (OTH)

AF:

0.000948

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00195

Hom.:

Bravo

AF:

0.00202

ESP6500AA

AF:

0.00477

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000453

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

BUB1B-related disorder (1)

Inborn genetic diseases (1)

Mosaic variegated aneuploidy syndrome 1 (1)

not provided (1)

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.82

CADD

Benign

9.1

(source)

DANN

Benign

0.69

DEOGEN2

Benign

0.077

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0025

LIST_S2

Benign

0.59

M_CAP

Benign

0.0023

MetaRNN

Benign

0.0029

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.4

PhyloP100

-0.41

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.28

REVEL

Benign

0.076

Sift

Benign

0.33

Sift4G

Benign

0.50

Polyphen

0.0

Vest4

0.027

MVP

0.59

MPC

0.20

ClinPred

0.0089

GERP RS

-5.2

PromoterAI

0.018

Neutral

(source)

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.048

gMVP

0.13

Mutation Taster

=92/8

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over