Variant rs1129352 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001211.6(BUB1B):c.1623T>C(p.Asn541=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00402 in 1,612,164 control chromosomes in the GnomAD database, including 237 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 115 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 122 hom. )

Consequence

BUB1B
NM_001211.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.702

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 15-40202460-T-C is Benign according to our data. Variant chr15-40202460-T-C is described in ClinVar as [Benign]. Clinvar id is 257633.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.702 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0751 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.1623T>C	p.Asn541=	synonymous_variant	13/23	ENST00000287598.11
LOC107984763	XR_001751506.2 linkuse as main transcript	n.218-22259A>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.1623T>C	p.Asn541=	synonymous_variant	13/23	1	NM_001211.6	P1	O60566-1
BUB1B	ENST00000412359.7 linkuse as main transcript	c.1665T>C	p.Asn555=	synonymous_variant	13/23	2			O60566-3
BUB1B	ENST00000558972.1 linkuse as main transcript	n.428T>C		non_coding_transcript_exon_variant	3/5	3
BUB1B	ENST00000559733.5 linkuse as main transcript	c.*536T>C		3_prime_UTR_variant, NMD_transcript_variant	6/7	3

Frequencies

GnomAD3 genomes

AF:

0.0220

AC:

3354

AN:

152136

Hom.:

115

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0774

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00701

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:

0.000118

Gnomad OTH

AF:

0.0158

GnomAD3 exomes

AF:

0.00549

AC:

1374

AN:

250054

Hom.:

AF XY:

0.00435

AC XY:

588

AN XY:

135244

show subpopulations

Gnomad AFR exome

AF:

0.0781

Gnomad AMR exome

AF:

0.00247

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000330

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000133

Gnomad OTH exome

AF:

0.00246

GnomAD4 exome

AF:

0.00214

AC:

3124

AN:

1459910

Hom.:

122

Cov.:

AF XY:

0.00180

AC XY:

1304

AN XY:

726296

show subpopulations

Gnomad4 AFR exome

AF:

0.0788

Gnomad4 AMR exome

AF:

0.00332

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000932

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000549

Gnomad4 OTH exome

AF:

0.00459

GnomAD4 genome

AF:

0.0221

AC:

3360

AN:

152254

Hom.:

115

Cov.:

AF XY:

0.0214

AC XY:

1594

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0773

Gnomad4 AMR

AF:

0.00700

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.0156

Alfa

AF:

0.0120

Hom.:

Bravo

AF:

0.0250

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 24, 2019	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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 28, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.8

DANN

Benign

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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