rs1802286

Positions:

chr15-40218461-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001211.6(BUB1B):c.2856C>T(p.Asp952=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0253 in 1,610,922 control chromosomes in the GnomAD database, including 653 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 57 hom., cov: 32)

Exomes 𝑓: 0.026 ( 596 hom. )

Consequence

BUB1B
NM_001211.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.77

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-PAK6 (HGNC:):

BUB1B-PAK6 links:

PAK6 (HGNC:16061): (p21 (RAC1) activated kinase 6) This gene encodes a member of a family of p21-stimulated serine/threonine protein kinases, which contain an amino-terminal Cdc42/Rac interactive binding (CRIB) domain and a carboxyl-terminal kinase domain. These kinases function in a number of cellular processes, including cytoskeleton rearrangement, apoptosis, and the mitogen-activated protein (MAP) kinase signaling pathway. The protein encoded by this gene interacts with androgen receptor (AR) and translocates to the nucleus, where it is involved in transcriptional regulation. Changes in expression of this gene have been linked to prostate cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

PAK6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 15-40218461-C-T is Benign according to our data. Variant chr15-40218461-C-T is described in ClinVar as [Benign]. Clinvar id is 224924.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-40218461-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.77 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0218 (3316/152282) while in subpopulation NFE AF= 0.0305 (2072/68024). AF 95% confidence interval is 0.0294. There are 57 homozygotes in gnomad4. There are 1693 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 57 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
BUB1B	NM_001211.6 linkuse as main transcript	c.2856C>T	p.Asp952=	synonymous_variant	22/23	ENST00000287598.11
BUB1B-PAK6	NM_001128628.3 linkuse as main transcript	c.-201+794C>T		intron_variant
LOC107984763	XR_001751506.2 linkuse as main transcript	n.217+21024G>A		intron_variant, non_coding_transcript_variant
BUB1B-PAK6	NM_001128629.3 linkuse as main transcript	c.-118+794C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BUB1B	ENST00000287598.11 linkuse as main transcript	c.2856C>T	p.Asp952=	synonymous_variant	22/23	1	NM_001211.6	P1	O60566-1

Frequencies

GnomAD3 genomes

AF:

0.0218

AC:

3315

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00509

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00897

Gnomad ASJ

AF:

0.0331

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00807

Gnomad FIN

AF:

0.0651

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0305

Gnomad OTH

AF:

0.0215

GnomAD3 exomes

AF:

0.0237

AC:

5928

AN:

250472

Hom.:

123

AF XY:

0.0240

AC XY:

3243

AN XY:

135332

show subpopulations

Gnomad AFR exome

AF:

0.00481

Gnomad AMR exome

AF:

0.0125

Gnomad ASJ exome

AF:

0.0308

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0112

Gnomad FIN exome

AF:

0.0613

Gnomad NFE exome

AF:

0.0290

Gnomad OTH exome

AF:

0.0264

GnomAD4 exome

AF:

0.0257

AC:

37498

AN:

1458640

Hom.:

596

Cov.:

AF XY:

0.0257

AC XY:

18632

AN XY:

725728

show subpopulations

Gnomad4 AFR exome

AF:

0.00413

Gnomad4 AMR exome

AF:

0.0129

Gnomad4 ASJ exome

AF:

0.0300

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0121

Gnomad4 FIN exome

AF:

0.0583

Gnomad4 NFE exome

AF:

0.0273

Gnomad4 OTH exome

AF:

0.0240

GnomAD4 genome

AF:

0.0218

AC:

3316

AN:

152282

Hom.:

Cov.:

AF XY:

0.0227

AC XY:

1693

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00508

Gnomad4 AMR

AF:

0.00896

Gnomad4 ASJ

AF:

0.0331

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00849

Gnomad4 FIN

AF:

0.0651

Gnomad4 NFE

AF:

0.0305

Gnomad4 OTH

AF:

0.0213

Alfa

AF:

0.0272

Hom.:

Bravo

AF:

0.0173

Asia WGS

AF:

0.00404

AC:

AN:

3476

EpiCase

AF:

0.0338

EpiControl

AF:

0.0297

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -

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

Feb 11, 2019

- -

Mosaic variegated aneuploidy syndrome 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

5.3

DANN

Benign

0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

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