rs1801389

chr15-40170579-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001211.6(BUB1B):c.282G>A(p.Lys94=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 1,612,750 control chromosomes in the GnomAD database, including 15,827 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1487 hom., cov: 32)
  • Exomes 𝑓: 0.14 (14340 hom.)
• Consequence: BUB1B NM_001211.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.565

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]

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant 15-40170579-G-A is Benign according to our data. Variant chr15-40170579-G-A is described in ClinVar as [Benign]. Clinvar id is 257637.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.565 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BUB1B	NM_001211.6	c.282G>A	p.Lys94=	synonymous_variant	4/23	ENST00000287598.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BUB1B	ENST00000287598.11	c.282G>A	p.Lys94=	synonymous_variant	4/23	1	NM_001211.6	P1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20301 AN: 152106 Hom.: 1485 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.0990

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.00443

Gnomad SAS AF: 0.0594

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.118

GnomAD3 exomes AF: 0.120 AC: 30049 AN: 251352 Hom.: 2231 AF XY: 0.119 AC XY: 16117 AN XY: 135846

Gnomad AFR exome AF: 0.127

Gnomad AMR exome AF: 0.0719

Gnomad ASJ exome AF: 0.186

Gnomad EAS exome AF: 0.00430

Gnomad SAS exome AF: 0.0602

Gnomad FIN exome AF: 0.178

Gnomad NFE exome AF: 0.150

Gnomad OTH exome AF: 0.128

GnomAD4 exome AF: 0.135 AC: 197383 AN: 1460526 Hom.: 14340 Cov.: 33 AF XY: 0.133 AC XY: 96392 AN XY: 726660

Gnomad4 AFR exome AF: 0.131

Gnomad4 AMR exome AF: 0.0758

Gnomad4 ASJ exome AF: 0.186

Gnomad4 EAS exome AF: 0.00421

Gnomad4 SAS exome AF: 0.0607

Gnomad4 FIN exome AF: 0.176

Gnomad4 NFE exome AF: 0.145

Gnomad4 OTH exome AF: 0.130

GnomAD4 genome AF: 0.133 AC: 20315 AN: 152224 Hom.: 1487 Cov.: 32 AF XY: 0.133 AC XY: 9871 AN XY: 74434

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.0987

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.00425

Gnomad4 SAS AF: 0.0588

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.117

Alfa AF: 0.141 Hom.: 2584

Bravo AF: 0.128

Asia WGS AF: 0.0460 AC: 160 AN: 3478

EpiCase AF: 0.146

EpiControl AF: 0.142

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 10, 2019

- -

Mosaic variegated aneuploidy syndrome 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
Cadd	Benign	7.9
Dann	Benign	0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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

Other links and lift over

dbSNP: rs1801389; hg19: chr15-40462780; COSMIC: COSV55009514;