rs1017842

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001211.6(BUB1B):c.1170G>C(p.Glu390Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00644 in 1,612,070 control chromosomes in the GnomAD database, including 558 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.034 ( 291 hom., cov: 32)

Exomes 𝑓: 0.0036 ( 267 hom. )

Consequence

BUB1B
NM_001211.6 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.646

Publications

13 publications found

Variant links:

COSMIC-nc: COSV55010791

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

BUB1B links:

LOC107984763 (HGNC:):

LOC107984763 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0010971129).

BP6

Variant 15-40196656-G-C is Benign according to our data. Variant chr15-40196656-G-C is described in ClinVar as Benign. ClinVar VariationId is 133782.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BUB1B	NM_001211.6 link	c.1170G>C	p.Glu390Asp	missense_variant	Exon 9 of 23	ENST00000287598.11	NP_001202.5	O60566-1
LOC107984763	XR_001751506.2 link	n.218-16455C>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BUB1B	ENST00000287598.11 link	c.1170G>C	p.Glu390Asp	missense_variant	Exon 9 of 23	1	NM_001211.6	ENSP00000287598.7		O60566-1
BUB1B	ENST00000412359.7 link	c.1212G>C	p.Glu404Asp	missense_variant	Exon 9 of 23	2		ENSP00000398470.3		O60566-3

Frequencies

GnomAD3 genomes

AF:

0.0338

AC:

5142

AN:

152018

Hom.:

291

Cov.:

show subpopulations

Gnomad AFR

AF:

0.118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0103

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000633

Gnomad OTH

AF:

0.0272

GnomAD2 exomes

AF:

0.00883

AC:

2218

AN:

251258

AF XY:

0.00652

show subpopulations

Gnomad AFR exome

AF:

0.120

Gnomad AMR exome

AF:

0.00575

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000449

Gnomad OTH exome

AF:

0.00375

GnomAD4 exome

AF:

0.00358

AC:

5231

AN:

1459934

Hom.:

267

Cov.:

AF XY:

0.00311

AC XY:

2257

AN XY:

726280

show subpopulations

African (AFR)

AF:

0.125

AC:

4178

AN:

33468

American (AMR)

AF:

0.00625

AC:

279

AN:

44668

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.000174

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00520

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000254

AC:

282

AN:

1110208

Other (OTH)

AF:

0.00741

AC:

447

AN:

60334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

267

533

800

1066

1333

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

138

276

414

552

690

<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:

0.0339

AC:

5153

AN:

152136

Hom.:

291

Cov.:

AF XY:

0.0323

AC XY:

2400

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.118

AC:

4894

AN:

41532

American (AMR)

AF:

0.0103

AC:

157

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000633

AC:

AN:

67936

Other (OTH)

AF:

0.0270

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

236

472

709

945

1181

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

156

208

260

<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:

0.00268

Hom.:

Bravo

AF:

0.0384

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.116

AC:

509

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.0109

AC:

1317

Asia WGS

AF:

0.00722

AC:

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.000474

ClinVar

Significance: Benign

Submissions summary: Benign:5Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 28, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Colorectal cancer

Benign:1

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Premature chromatid separation trait

Benign:1

Feb 01, 2025

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mosaic variegated aneuploidy syndrome 1

Benign:1

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Other:1

Sep 19, 2013

ITMI

Significance:not provided

Review Status:no classification provided

Collection Method:reference population

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.55

CADD

Benign

9.6

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.089

T;.

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.70

T;T

MetaRNN

Benign

0.0011

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

M;.

PhyloP100

-0.65

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.53

N;N

REVEL

Benign

0.0070

Sift

Benign

0.29

T;T

Sift4G

Benign

0.094

T;T

Polyphen

0.10

B;B

Vest4

0.037

MutPred

0.20

Loss of helix (P = 0.079);.;

MPC

0.20

ClinPred

0.0072

GERP RS

0.26

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.027

gMVP

0.14

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over