rs28989189

Positions:

chr15-40170645-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001211.6(BUB1B):c.348T>C(p.Tyr116Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00932 in 1,613,708 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0060 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0097 ( 110 hom. )

Consequence

BUB1B
NM_001211.6 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.162

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 15-40170645-T-C is Benign according to our data. Variant chr15-40170645-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 238666.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-40170645-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.162 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00603 (918/152326) while in subpopulation NFE AF= 0.00966 (657/68030). AF 95% confidence interval is 0.00905. There are 4 homozygotes in gnomad4. There are 422 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BUB1B	NM_001211.6 linkuse as main transcript	c.348T>C	p.Tyr116Tyr	synonymous_variant	4/23	ENST00000287598.11	NP_001202.5	O60566-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BUB1B	ENST00000287598.11 linkuse as main transcript	c.348T>C	p.Tyr116Tyr	synonymous_variant	4/23	1	NM_001211.6	ENSP00000287598.7		O60566-1
BUB1B	ENST00000412359.7 linkuse as main transcript	c.390T>C	p.Tyr130Tyr	synonymous_variant	4/23	2		ENSP00000398470.3		O60566-3

Frequencies

GnomAD3 genomes

AF:

0.00602

AC:

917

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00195

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.00288

Gnomad ASJ

AF:

0.0138

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00828

Gnomad FIN

AF:

0.00226

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.00966

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00694

AC:

1745

AN:

251348

Hom.:

AF XY:

0.00727

AC XY:

987

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.00172

Gnomad AMR exome

AF:

0.00335

Gnomad ASJ exome

AF:

0.0134

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00859

Gnomad FIN exome

AF:

0.00287

Gnomad NFE exome

AF:

0.00961

Gnomad OTH exome

AF:

0.00783

GnomAD4 exome

AF:

0.00967

AC:

14127

AN:

1461382

Hom.:

110

Cov.:

AF XY:

0.00961

AC XY:

6984

AN XY:

727022

show subpopulations

Gnomad4 AFR exome

AF:

0.00146

Gnomad4 AMR exome

AF:

0.00356

Gnomad4 ASJ exome

AF:

0.0137

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00794

Gnomad4 FIN exome

AF:

0.00375

Gnomad4 NFE exome

AF:

0.0108

Gnomad4 OTH exome

AF:

0.00919

GnomAD4 genome

AF:

0.00603

AC:

918

AN:

152326

Hom.:

Cov.:

AF XY:

0.00566

AC XY:

422

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00195

Gnomad4 AMR

AF:

0.00288

Gnomad4 ASJ

AF:

0.0138

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00850

Gnomad4 FIN

AF:

0.00226

Gnomad4 NFE

AF:

0.00966

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00906

Hom.:

Bravo

AF:

0.00583

Asia WGS

AF:

0.00260

AC:

AN:

3476

EpiCase

AF:

0.0117

EpiControl

AF:

0.0114

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 14, 2020	This variant is associated with the following publications: (PMID: 16182441) -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	BUB1B: BP4, BP7, BS1, BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 05, 2017

- -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 12, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Colorectal cancer

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Mosaic variegated aneuploidy syndrome 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

5.5

DANN

Benign

0.39

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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