Variant rs141013408 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001211.6(BUB1B):c.1371A>C(p.Gln457His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q457P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

BUB1B
NM_001211.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.349

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 links:

LOC107984763 (HGNC:):

LOC107984763 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2511428).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BUB1B	NM_001211.6 linkuse as main transcript	c.1371A>C	p.Gln457His	missense_variant	10/23	ENST00000287598.11
LOC107984763	XR_001751506.2 linkuse as main transcript	n.218-19496T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BUB1B	ENST00000287598.11 linkuse as main transcript	c.1371A>C	p.Gln457His	missense_variant	10/23	1	NM_001211.6	P1	O60566-1
BUB1B	ENST00000412359.7 linkuse as main transcript	c.1413A>C	p.Gln471His	missense_variant	10/23	2			O60566-3
BUB1B	ENST00000559772.1 linkuse as main transcript	n.484A>C		non_coding_transcript_exon_variant	3/4	4
BUB1B	ENST00000559733.5 linkuse as main transcript	c.*284A>C		3_prime_UTR_variant, NMD_transcript_variant	3/7	3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251328

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Benign

0.21

T;.

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.72

T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.25

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.6

M;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.19

Sift

Uncertain

0.015

D;D

Sift4G

Benign

0.071

T;T

Polyphen

1.0

D;D

Vest4

0.29

MutPred

0.097

Loss of helix (P = 0.0376);.;

MVP

0.82

MPC

0.67

ClinPred

0.72

GERP RS

-4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.056

gMVP

0.33

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over