NM_001211.6:c.36-13dupT

Variant names:

• chr15-40165037-G-GT
• rs150031754
• NM_001211.6:c.36-13dupT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001211.6(BUB1B):​c.36-13dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 1,613,942 control chromosomes in the GnomAD database, including 1,685 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.059 (876 hom., cov: 32)
  • Exomes 𝑓: 0.0067 (809 hom.)
• Consequence: BUB1B NM_001211.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.838
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• mosaic variegated aneuploidy syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen, G2P
• rhabdomyosarcoma

  Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
• mosaic variegated aneuploidy syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 15-40165037-G-GT is Benign according to our data. Variant chr15-40165037-G-GT is described in ClinVar as Benign. ClinVar VariationId is 257639.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001211.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BUB1B	NM_001211.6	MANE Select	c.36-13dupT		intron	N/A	NP_001202.5

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BUB1B	ENST00000287598.11	TSL:1 MANE Select	c.36-16_36-15insT		intron	N/A	ENSP00000287598.7
	BUB1B	ENST00000412359.7	TSL:2	c.36-16_36-15insT		intron	N/A	ENSP00000398470.3
	BUB1B	ENST00000918306.1		c.36-16_36-15insT		intron	N/A	ENSP00000588365.1

Frequencies

GnomAD3 genomes AF: 0.0591 AC: 8985 AN: 152082 Hom.: 872 Cov.: 32

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0211

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00119

Gnomad OTH AF: 0.0449

GnomAD2 exomes AF: 0.0157 AC: 3948 AN: 251402 AF XY: 0.0117

Gnomad AFR exome AF: 0.207

Gnomad AMR exome AF: 0.00977

Gnomad ASJ exome AF: 0.00635

Gnomad EAS exome AF: 0.000217

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00106

Gnomad OTH exome AF: 0.00896

GnomAD4 exome AF: 0.00666 AC: 9730 AN: 1461742 Hom.: 809 Cov.: 31 AF XY: 0.00590 AC XY: 4289 AN XY: 727184

African (AFR) AF: 0.212 AC: 7105 AN: 33458

American (AMR) AF: 0.0114 AC: 509 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00566 AC: 148 AN: 26136

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39696

South Asian (SAS) AF: 0.000464 AC: 40 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53378

Middle Eastern (MID) AF: 0.0125 AC: 72 AN: 5764

European-Non Finnish (NFE) AF: 0.000862 AC: 959 AN: 1111938

Other (OTH) AF: 0.0148 AC: 894 AN: 60392

GnomAD4 genome AF: 0.0593 AC: 9023 AN: 152200 Hom.: 876 Cov.: 32 AF XY: 0.0575 AC XY: 4277 AN XY: 74412

African (AFR) AF: 0.205 AC: 8500 AN: 41490

American (AMR) AF: 0.0210 AC: 321 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00548 AC: 19 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00119 AC: 81 AN: 68024

Other (OTH) AF: 0.0444 AC: 94 AN: 2116

Alfa AF: 0.0213 Hom.: 60

Bravo AF: 0.0673

Asia WGS AF: 0.0180 AC: 62 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Mosaic variegated aneuploidy syndrome 1 (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.84
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs150031754; hg19: chr15-40457238;