chr15-40208785-C-T

Variant names:

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.2143+15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 1,599,102 control chromosomes in the GnomAD database, including 226,339 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 17323 hom., cov: 31)

Exomes 𝑓: 0.53 ( 209016 hom. )

Consequence

BUB1B
NM_001211.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.522

Publications

6 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:

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 (BayesDel_noAF=-0.83).

BP6

Variant 15-40208785-C-T is Benign according to our data. Variant chr15-40208785-C-T is described in ClinVar as Benign. ClinVar VariationId is 257634.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BUB1B	NM_001211.6 link	c.2143+15C>T		intron_variant	Intron 16 of 22	ENST00000287598.11	NP_001202.5
LOC107984763	XR_001751506.2 link	n.218-28584G>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BUB1B	ENST00000287598.11 link	c.2143+15C>T		intron_variant	Intron 16 of 22	1	NM_001211.6	ENSP00000287598.7
BUB1B	ENST00000412359.7 link	c.2185+15C>T		intron_variant	Intron 16 of 22	2		ENSP00000398470.3

Frequencies

GnomAD3 genomes

AF:

0.463

AC:

70222

AN:

151798

Hom.:

17310

Cov.:

show subpopulations

Gnomad AFR

AF:

0.301

Gnomad AMI

AF:

0.636

Gnomad AMR

AF:

0.479

Gnomad ASJ

AF:

0.401

Gnomad EAS

AF:

0.259

Gnomad SAS

AF:

0.478

Gnomad FIN

AF:

0.557

Gnomad MID

AF:

0.433

Gnomad NFE

AF:

0.559

Gnomad OTH

AF:

0.441

GnomAD2 exomes

AF:

0.493

AC:

123325

AN:

250390

AF XY:

0.497

show subpopulations

Gnomad AFR exome

AF:

0.298

Gnomad AMR exome

AF:

0.506

Gnomad ASJ exome

AF:

0.401

Gnomad EAS exome

AF:

0.248

Gnomad FIN exome

AF:

0.558

Gnomad NFE exome

AF:

0.556

Gnomad OTH exome

AF:

0.489

GnomAD4 exome

AF:

0.533

AC:

770770

AN:

1447184

Hom.:

209016

Cov.:

AF XY:

0.533

AC XY:

383961

AN XY:

720986

show subpopulations

African (AFR)

AF:

0.294

AC:

9775

AN:

33246

American (AMR)

AF:

0.507

AC:

22658

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.395

AC:

10292

AN:

26068

East Asian (EAS)

AF:

0.282

AC:

11160

AN:

39630

South Asian (SAS)

AF:

0.481

AC:

41327

AN:

85946

European-Finnish (FIN)

AF:

0.558

AC:

29363

AN:

52648

Middle Eastern (MID)

AF:

0.406

AC:

2329

AN:

5734

European-Non Finnish (NFE)

AF:

0.559

AC:

614321

AN:

1099280

Other (OTH)

AF:

0.493

AC:

29545

AN:

59938

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

16457

32915

49372

65830

82287

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16888

33776

50664

67552

84440

<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:

0.463

AC:

70267

AN:

151918

Hom.:

17323

Cov.:

AF XY:

0.461

AC XY:

34243

AN XY:

74220

show subpopulations

African (AFR)

AF:

0.301

AC:

12456

AN:

41446

American (AMR)

AF:

0.480

AC:

7334

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.401

AC:

1392

AN:

3470

East Asian (EAS)

AF:

0.259

AC:

1332

AN:

5150

South Asian (SAS)

AF:

0.479

AC:

2302

AN:

4808

European-Finnish (FIN)

AF:

0.557

AC:

5859

AN:

10516

Middle Eastern (MID)

AF:

0.431

AC:

125

AN:

290

European-Non Finnish (NFE)

AF:

0.559

AC:

37950

AN:

67944

Other (OTH)

AF:

0.444

AC:

938

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1813

3627

5440

7254

9067

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

640

1280

1920

2560

3200

<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:

0.386

Hom.:

3339

Bravo

AF:

0.447

Asia WGS

AF:

0.356

AC:

1238

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

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

- -

Mosaic variegated aneuploidy syndrome 1

Benign:2

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.5

(source)

DANN

Benign

0.30

PhyloP100

-0.52

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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