15-40220705-A-G

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.3099A>G(p.Lys1033Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0157 in 1,614,064 control chromosomes in the GnomAD database, including 3,213 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.082 ( 1688 hom., cov: 32)

Exomes 𝑓: 0.0088 ( 1525 hom. )

Consequence

BUB1B
NM_001211.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.91

Publications

3 publications found

Variant links:

COSMIC-nc: COSV104598940

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 links:

BUB1B-PAK6 (HGNC:52276): (BUB1B-PAK6 readthrough) This gene represents readthrough transcription between the genes BUB1B (mitotic checkpoint serine/threonine-protein kinase BUB1 beta) and PAK6 (serine/threonine-protein kinase PAK 6). The protein encoded by the readthrough transcripts is the same as the product of the downstream gene (PAK6). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

BUB1B-PAK6 links:

PAK6 (HGNC:16061): (p21 (RAC1) activated kinase 6) This gene encodes a member of a family of p21-stimulated serine/threonine protein kinases, which contain an amino-terminal Cdc42/Rac interactive binding (CRIB) domain and a carboxyl-terminal kinase domain. These kinases function in a number of cellular processes, including cytoskeleton rearrangement, apoptosis, and the mitogen-activated protein (MAP) kinase signaling pathway. The protein encoded by this gene interacts with androgen receptor (AR) and translocates to the nucleus, where it is involved in transcriptional regulation. Changes in expression of this gene have been linked to prostate cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

PAK6 links:

LOC107984763 (HGNC:):

LOC107984763 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=-0.46).

BP6

Variant 15-40220705-A-G is Benign according to our data. Variant chr15-40220705-A-G is described in ClinVar as Benign. ClinVar VariationId is 257638.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.91 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
BUB1B	NM_001211.6 link	c.3099A>G	p.Lys1033Lys	synonymous_variant	Exon 23 of 23	ENST00000287598.11	NP_001202.5
BUB1B-PAK6	NM_001128628.3 link	c.-201+3038A>G		intron_variant	Intron 1 of 10		NP_001122100.1
BUB1B-PAK6	NM_001128629.3 link	c.-118+3038A>G		intron_variant	Intron 1 of 9		NP_001122101.1
LOC107984763	XR_001751506.2 link	n.217+18780T>C		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
BUB1B	ENST00000287598.11 link	c.3099A>G	p.Lys1033Lys	synonymous_variant	Exon 23 of 23	1	NM_001211.6	ENSP00000287598.7
BUB1B	ENST00000412359.7 link	c.3141A>G	p.Lys1047Lys	synonymous_variant	Exon 23 of 23	2		ENSP00000398470.3
BUB1B-PAK6	ENST00000559435.1 link	n.204A>G		non_coding_transcript_exon_variant	Exon 2 of 6	5		ENSP00000457109.1

Frequencies

GnomAD3 genomes

AF:

0.0816

AC:

12416

AN:

152082

Hom.:

1673

Cov.:

show subpopulations

Gnomad AFR

AF:

0.284

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0282

Gnomad ASJ

AF:

0.00547

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00132

Gnomad OTH

AF:

0.0608

GnomAD2 exomes

AF:

0.0212

AC:

5342

AN:

251486

AF XY:

0.0160

show subpopulations

Gnomad AFR exome

AF:

0.286

Gnomad AMR exome

AF:

0.0123

Gnomad ASJ exome

AF:

0.00635

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00120

Gnomad OTH exome

AF:

0.0109

GnomAD4 exome

AF:

0.00885

AC:

12932

AN:

1461864

Hom.:

1525

Cov.:

AF XY:

0.00774

AC XY:

5627

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.293

AC:

9795

AN:

33470

American (AMR)

AF:

0.0148

AC:

664

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00566

AC:

148

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.000580

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.0137

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000911

AC:

1013

AN:

1112008

Other (OTH)

AF:

0.0196

AC:

1183

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

630

1259

1889

2518

3148

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

298

596

894

1192

1490

<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:

0.0819

AC:

12468

AN:

152200

Hom.:

1688

Cov.:

AF XY:

0.0795

AC XY:

5915

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.284

AC:

11795

AN:

41470

American (AMR)

AF:

0.0281

AC:

429

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00547

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.000829

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00132

AC:

AN:

68026

Other (OTH)

AF:

0.0601

AC:

127

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

449

898

1348

1797

2246

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

220

330

440

550

<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:

0.0350

Hom.:

459

Bravo

AF:

0.0930

Asia WGS

AF:

0.0200

AC:

AN:

3478

EpiCase

AF:

0.00180

EpiControl

AF:

0.00190

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Apr 24, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

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

-0.46

CADD

Benign

(source)

DANN

Benign

0.87

PhyloP100

1.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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