15-40185630-G-A

Position:

chr15-40185630-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001211.6(BUB1B):c.1046G>A(p.Arg349Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 1,612,848 control chromosomes in the GnomAD database, including 385,531 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.71 ( 39490 hom., cov: 32)

Exomes 𝑓: 0.68 ( 346041 hom. )

Consequence

BUB1B
NM_001211.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: 3.42

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:

BUB1B (HGNC:):

BUB1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.3588683E-7).

BP6

Variant 15-40185630-G-A is Benign according to our data. Variant chr15-40185630-G-A is described in ClinVar as [Benign]. Clinvar id is 133780.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-40185630-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BUB1B	NM_001211.6 linkuse as main transcript	c.1046G>A	p.Arg349Gln	missense_variant	8/23	ENST00000287598.11	NP_001202.5	O60566-1
LOC107984763	XR_001751506.2 linkuse as main transcript	n.218-5429C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BUB1B	ENST00000287598.11 linkuse as main transcript	c.1046G>A	p.Arg349Gln	missense_variant	8/23	1	NM_001211.6	ENSP00000287598.7		O60566-1
BUB1B	ENST00000412359.7 linkuse as main transcript	c.1088G>A	p.Arg363Gln	missense_variant	8/23	2		ENSP00000398470.3		O60566-3

Frequencies

GnomAD3 genomes

AF:

0.712

AC:

108322

AN:

152044

Hom.:

39444

Cov.:

show subpopulations

Gnomad AFR

AF:

0.824

Gnomad AMI

AF:

0.846

Gnomad AMR

AF:

0.629

Gnomad ASJ

AF:

0.596

Gnomad EAS

AF:

0.329

Gnomad SAS

AF:

0.547

Gnomad FIN

AF:

0.739

Gnomad MID

AF:

0.582

Gnomad NFE

AF:

0.707

Gnomad OTH

AF:

0.644

GnomAD3 exomes

AF:

0.650

AC:

163454

AN:

251422

Hom.:

55071

AF XY:

0.645

AC XY:

87634

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.826

Gnomad AMR exome

AF:

0.611

Gnomad ASJ exome

AF:

0.593

Gnomad EAS exome

AF:

0.323

Gnomad SAS exome

AF:

0.544

Gnomad FIN exome

AF:

0.736

Gnomad NFE exome

AF:

0.708

Gnomad OTH exome

AF:

0.638

GnomAD4 exome

AF:

0.683

AC:

998301

AN:

1460684

Hom.:

346041

Cov.:

AF XY:

0.679

AC XY:

493532

AN XY:

726704

show subpopulations

Gnomad4 AFR exome

AF:

0.826

Gnomad4 AMR exome

AF:

0.618

Gnomad4 ASJ exome

AF:

0.586

Gnomad4 EAS exome

AF:

0.350

Gnomad4 SAS exome

AF:

0.549

Gnomad4 FIN exome

AF:

0.733

Gnomad4 NFE exome

AF:

0.706

Gnomad4 OTH exome

AF:

0.658

GnomAD4 genome

AF:

0.713

AC:

108435

AN:

152164

Hom.:

39490

Cov.:

AF XY:

0.706

AC XY:

52549

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.824

Gnomad4 AMR

AF:

0.629

Gnomad4 ASJ

AF:

0.596

Gnomad4 EAS

AF:

0.329

Gnomad4 SAS

AF:

0.547

Gnomad4 FIN

AF:

0.739

Gnomad4 NFE

AF:

0.707

Gnomad4 OTH

AF:

0.647

Alfa

AF:

0.695

Hom.:

95348

Bravo

AF:

0.709

TwinsUK

AF:

0.703

AC:

2607

ALSPAC

AF:

0.703

AC:

2708

ESP6500AA

AF:

0.814

AC:

3587

ESP6500EA

AF:

0.696

AC:

5985

ExAC

AF:

0.656

AC:

79710

Asia WGS

AF:

0.483

AC:

1681

AN:

3478

EpiCase

AF:

0.693

EpiControl

AF:

0.690

ClinVar

Significance: Benign

Submissions summary: Benign:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Mosaic variegated aneuploidy syndrome 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified

Benign:1Other:1

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	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, no classification provided	reference population	ITMI	Sep 19, 2013	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.047

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.30

DEOGEN2

Benign

0.088

T;.

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.054

LIST_S2

Benign

0.47

T;T

MetaRNN

Benign

7.4e-7

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-2.3

N;.

PrimateAI

Benign

0.43

PROVEAN

Benign

2.2

N;N

REVEL

Benign

0.061

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.18

MPC

0.23

ClinPred

0.012

GERP RS

4.7

Varity_R

0.022

gMVP

0.062

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over