Genetic Variant BUB1B:c.2678+1568T>G (chr15-40215042-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001211.6(BUB1B):c.2678+1568T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,146 control chromosomes in the GnomAD database, including 1,737 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.14 ( 1737 hom., cov: 30)

Consequence

BUB1B
NM_001211.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.146

Publications

1 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BUB1B	NM_001211.6 link	c.2678+1568T>G		intron_variant	Intron 20 of 22	ENST00000287598.11	NP_001202.5
LOC107984763	XR_001751506.2 link	n.217+24443A>C		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BUB1B	ENST00000287598.11 link	c.2678+1568T>G		intron_variant	Intron 20 of 22	1	NM_001211.6	ENSP00000287598.7
BUB1B	ENST00000412359.7 link	c.2720+1568T>G		intron_variant	Intron 20 of 22	2		ENSP00000398470.3

Frequencies

GnomAD3 genomes

AF:

0.144

AC:

21936

AN:

152028

Hom.:

1734

Cov.:

show subpopulations

Gnomad AFR

AF:

0.179

Gnomad AMI

AF:

0.209

Gnomad AMR

AF:

0.102

Gnomad ASJ

AF:

0.179

Gnomad EAS

AF:

0.00442

Gnomad SAS

AF:

0.0624

Gnomad FIN

AF:

0.179

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.142

Gnomad OTH

AF:

0.126

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.144

AC:

21953

AN:

152146

Hom.:

1737

Cov.:

AF XY:

0.143

AC XY:

10615

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.180

AC:

7447

AN:

41476

American (AMR)

AF:

0.102

AC:

1553

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.179

AC:

622

AN:

3472

East Asian (EAS)

AF:

0.00424

AC:

AN:

5190

South Asian (SAS)

AF:

0.0618

AC:

298

AN:

4822

European-Finnish (FIN)

AF:

0.179

AC:

1889

AN:

10570

Middle Eastern (MID)

AF:

0.133

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.142

AC:

9630

AN:

68018

Other (OTH)

AF:

0.125

AC:

263

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

946

1892

2837

3783

4729

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

242

484

726

968

1210

<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:

0.0923

Hom.:

137

Bravo

AF:

0.141

Asia WGS

AF:

0.0500

AC:

174

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.3

(source)

DANN

Benign

0.68

PhyloP100

-0.15

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over