rs1047130

chr15-40196650-G-Achr15-40196650-G-Cchr15-40196650-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001211.6(BUB1B):c.1164G>A(p.Ala388=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 1,613,594 control chromosomes in the GnomAD database, including 72,408 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A388A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.23 (4968 hom., cov: 32)
  • Exomes 𝑓: 0.30 (67440 hom.)
• Consequence: BUB1B NM_001211.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.553

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]

LOC107984763 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 15-40196650-G-A is Benign according to our data. Variant chr15-40196650-G-A is described in ClinVar as [Benign]. Clinvar id is 257632.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-40196650-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.553 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BUB1B	NM_001211.6	c.1164G>A	p.Ala388=	synonymous_variant	9/23	ENST00000287598.11
LOC107984763	XR_001751506.2	n.218-16449C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BUB1B	ENST00000287598.11	c.1164G>A	p.Ala388=	synonymous_variant	9/23	1	NM_001211.6	P1

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34970 AN: 151956 Hom.: 4962 Cov.: 32

Gnomad AFR AF: 0.0613

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.224

GnomAD3 exomes AF: 0.272 AC: 68292 AN: 251252 Hom.: 10213 AF XY: 0.273 AC XY: 37009 AN XY: 135796

Gnomad AFR exome AF: 0.0594

Gnomad AMR exome AF: 0.352

Gnomad ASJ exome AF: 0.185

Gnomad EAS exome AF: 0.146

Gnomad SAS exome AF: 0.237

Gnomad FIN exome AF: 0.285

Gnomad NFE exome AF: 0.313

Gnomad OTH exome AF: 0.261

GnomAD4 exome AF: 0.298 AC: 436060 AN: 1461518 Hom.: 67440 Cov.: 36 AF XY: 0.297 AC XY: 216066 AN XY: 727070

Gnomad4 AFR exome AF: 0.0514

Gnomad4 AMR exome AF: 0.349

Gnomad4 ASJ exome AF: 0.183

Gnomad4 EAS exome AF: 0.170

Gnomad4 SAS exome AF: 0.244

Gnomad4 FIN exome AF: 0.286

Gnomad4 NFE exome AF: 0.318

Gnomad4 OTH exome AF: 0.270

GnomAD4 genome AF: 0.230 AC: 34985 AN: 152076 Hom.: 4968 Cov.: 32 AF XY: 0.229 AC XY: 17020 AN XY: 74344

Gnomad4 AFR AF: 0.0612

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.188

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.315

Gnomad4 OTH AF: 0.224

Alfa AF: 0.289 Hom.: 8914

Bravo AF: 0.225

Asia WGS AF: 0.168 AC: 586 AN: 3478

EpiCase AF: 0.303

EpiControl AF: 0.296

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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	- -

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

Feb 02, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
Cadd	Benign	9.7
Dann	Benign	0.50
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

Other links and lift over

dbSNP: rs1047130; hg19: chr15-40488851; COSMIC: COSV55010434; COSMIC: COSV55010434;