15-40208785-C-T

Variant summary

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

The NM_001211.6(BUB1B):c.2143+15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 1,599,102 control chromosomes in the GnomAD database, including 226,339 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 17323 hom., cov: 31)

Exomes 𝑓: 0.53 ( 209016 hom. )

Consequence

BUB1B
NM_001211.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.522

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:

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 (BayesDel_noAF=-0.83).

BP6

Variant 15-40208785-C-T is Benign according to our data. Variant chr15-40208785-C-T is described in ClinVar as [Benign]. Clinvar id is 257634.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-40208785-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BUB1B	NM_001211.6 linkuse as main transcript	c.2143+15C>T		intron_variant		ENST00000287598.11
LOC107984763	XR_001751506.2 linkuse as main transcript	n.218-28584G>A		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.2143+15C>T		intron_variant		1	NM_001211.6	P1	O60566-1
BUB1B	ENST00000412359.7 linkuse as main transcript	c.2185+15C>T		intron_variant		2			O60566-3

Frequencies

GnomAD3 genomes

AF:

0.463

AC:

70222

AN:

151798

Hom.:

17310

Cov.:

show subpopulations

Gnomad AFR

AF:

0.301

Gnomad AMI

AF:

0.636

Gnomad AMR

AF:

0.479

Gnomad ASJ

AF:

0.401

Gnomad EAS

AF:

0.259

Gnomad SAS

AF:

0.478

Gnomad FIN

AF:

0.557

Gnomad MID

AF:

0.433

Gnomad NFE

AF:

0.559

Gnomad OTH

AF:

0.441

GnomAD3 exomes

AF:

0.493

AC:

123325

AN:

250390

Hom.:

31723

AF XY:

0.497

AC XY:

67268

AN XY:

135434

show subpopulations

Gnomad AFR exome

AF:

0.298

Gnomad AMR exome

AF:

0.506

Gnomad ASJ exome

AF:

0.401

Gnomad EAS exome

AF:

0.248

Gnomad SAS exome

AF:

0.477

Gnomad FIN exome

AF:

0.558

Gnomad NFE exome

AF:

0.556

Gnomad OTH exome

AF:

0.489

GnomAD4 exome

AF:

0.533

AC:

770770

AN:

1447184

Hom.:

209016

Cov.:

AF XY:

0.533

AC XY:

383961

AN XY:

720986

show subpopulations

Gnomad4 AFR exome

AF:

0.294

Gnomad4 AMR exome

AF:

0.507

Gnomad4 ASJ exome

AF:

0.395

Gnomad4 EAS exome

AF:

0.282

Gnomad4 SAS exome

AF:

0.481

Gnomad4 FIN exome

AF:

0.558

Gnomad4 NFE exome

AF:

0.559

Gnomad4 OTH exome

AF:

0.493

GnomAD4 genome

AF:

0.463

AC:

70267

AN:

151918

Hom.:

17323

Cov.:

AF XY:

0.461

AC XY:

34243

AN XY:

74220

show subpopulations

Gnomad4 AFR

AF:

0.301

Gnomad4 AMR

AF:

0.480

Gnomad4 ASJ

AF:

0.401

Gnomad4 EAS

AF:

0.259

Gnomad4 SAS

AF:

0.479

Gnomad4 FIN

AF:

0.557

Gnomad4 NFE

AF:

0.559

Gnomad4 OTH

AF:

0.444

Alfa

AF:

0.429

Hom.:

2593

Bravo

AF:

0.447

Asia WGS

AF:

0.356

AC:

1238

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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 -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Mosaic variegated aneuploidy syndrome 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -

Colorectal cancer

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

Cadd

Benign

1.5

Dann

Benign

0.30

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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