rs1801389

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001211.6(BUB1B):c.282G>A(p.Lys94Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 1,612,750 control chromosomes in the GnomAD database, including 15,827 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1487 hom., cov: 32)

Exomes 𝑓: 0.14 ( 14340 hom. )

Consequence

BUB1B
NM_001211.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.565

Publications

14 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: 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 15-40170579-G-A is Benign according to our data. Variant chr15-40170579-G-A is described in ClinVar as Benign. ClinVar VariationId is 257637.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.565 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BUB1B	NM_001211.6 link	c.282G>A	p.Lys94Lys	synonymous_variant	Exon 4 of 23	ENST00000287598.11	NP_001202.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BUB1B	ENST00000287598.11 link	c.282G>A	p.Lys94Lys	synonymous_variant	Exon 4 of 23	1	NM_001211.6	ENSP00000287598.7
BUB1B	ENST00000412359.7 link	c.324G>A	p.Lys108Lys	synonymous_variant	Exon 4 of 23	2		ENSP00000398470.3

Frequencies

GnomAD3 genomes

AF:

0.133

AC:

20301

AN:

152106

Hom.:

1485

Cov.:

show subpopulations

Gnomad AFR

AF:

0.131

Gnomad AMI

AF:

0.208

Gnomad AMR

AF:

0.0990

Gnomad ASJ

AF:

0.189

Gnomad EAS

AF:

0.00443

Gnomad SAS

AF:

0.0594

Gnomad FIN

AF:

0.182

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.147

Gnomad OTH

AF:

0.118

GnomAD2 exomes

AF:

0.120

AC:

30049

AN:

251352

AF XY:

0.119

show subpopulations

Gnomad AFR exome

AF:

0.127

Gnomad AMR exome

AF:

0.0719

Gnomad ASJ exome

AF:

0.186

Gnomad EAS exome

AF:

0.00430

Gnomad FIN exome

AF:

0.178

Gnomad NFE exome

AF:

0.150

Gnomad OTH exome

AF:

0.128

GnomAD4 exome

AF:

0.135

AC:

197383

AN:

1460526

Hom.:

14340

Cov.:

AF XY:

0.133

AC XY:

96392

AN XY:

726660

show subpopulations

African (AFR)

AF:

0.131

AC:

4377

AN:

33436

American (AMR)

AF:

0.0758

AC:

3388

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.186

AC:

4866

AN:

26120

East Asian (EAS)

AF:

0.00421

AC:

167

AN:

39648

South Asian (SAS)

AF:

0.0607

AC:

5231

AN:

86242

European-Finnish (FIN)

AF:

0.176

AC:

9379

AN:

53364

Middle Eastern (MID)

AF:

0.122

AC:

704

AN:

5764

European-Non Finnish (NFE)

AF:

0.145

AC:

161403

AN:

1110880

Other (OTH)

AF:

0.130

AC:

7868

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

8635

17270

25905

34540

43175

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5632

11264

16896

22528

28160

<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:

0.133

AC:

20315

AN:

152224

Hom.:

1487

Cov.:

AF XY:

0.133

AC XY:

9871

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.131

AC:

5456

AN:

41528

American (AMR)

AF:

0.0987

AC:

1510

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.189

AC:

655

AN:

3464

East Asian (EAS)

AF:

0.00425

AC:

AN:

5182

South Asian (SAS)

AF:

0.0588

AC:

284

AN:

4830

European-Finnish (FIN)

AF:

0.182

AC:

1925

AN:

10588

Middle Eastern (MID)

AF:

0.129

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.147

AC:

9987

AN:

68014

Other (OTH)

AF:

0.117

AC:

248

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

910

1820

2729

3639

4549

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

228

456

684

912

1140

<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:

0.140

Hom.:

3098

Bravo

AF:

0.128

Asia WGS

AF:

0.0460

AC:

160

AN:

3478

EpiCase

AF:

0.146

EpiControl

AF:

0.142

ClinVar

Significance: Benign

Submissions summary: Benign:6

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

- -

Jan 10, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

7.9

(source)

DANN

Benign

0.77

PhyloP100

0.56

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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