NM_001211.6:c.2284+17T>G

Variant names:

• chr15-40209792-T-G
• rs13380241
• NM_001211.6:c.2284+17T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001211.6(BUB1B):​c.2284+17T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0153 in 1,613,564 control chromosomes in the GnomAD database, including 2,977 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.079 (1562 hom., cov: 32)
  • Exomes 𝑓: 0.0086 (1415 hom.)
• Consequence: BUB1B NM_001211.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.316
• Publications: 2 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: ClinGen, Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae)
• rhabdomyosarcoma

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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

LOC107984763 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 15-40209792-T-G is Benign according to our data. Variant chr15-40209792-T-G is described in ClinVar as Benign. ClinVar VariationId is 257635.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.271 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BUB1B	NM_001211.6	MANE Select	c.2284+17T>G		intron	N/A	NP_001202.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BUB1B	ENST00000287598.11	TSL:1 MANE Select	c.2284+17T>G		intron	N/A	ENSP00000287598.7	O60566-1
	BUB1B	ENST00000412359.7	TSL:2	c.2326+17T>G		intron	N/A	ENSP00000398470.3	O60566-3
	BUB1B	ENST00000918306.1		c.2386+17T>G		intron	N/A	ENSP00000588365.1

Frequencies

GnomAD3 genomes AF: 0.0791 AC: 12037 AN: 152092 Hom.: 1551 Cov.: 32

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0273

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00134

Gnomad OTH AF: 0.0597

GnomAD2 exomes AF: 0.0205 AC: 5165 AN: 251408 AF XY: 0.0155

Gnomad AFR exome AF: 0.276

Gnomad AMR exome AF: 0.0120

Gnomad ASJ exome AF: 0.00635

Gnomad EAS exome AF: 0.000217

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00118

Gnomad OTH exome AF: 0.0106

GnomAD4 exome AF: 0.00857 AC: 12523 AN: 1461354 Hom.: 1415 Cov.: 32 AF XY: 0.00747 AC XY: 5429 AN XY: 727034

African (AFR) AF: 0.283 AC: 9452 AN: 33444

American (AMR) AF: 0.0144 AC: 645 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00567 AC: 148 AN: 26124

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39676

South Asian (SAS) AF: 0.000533 AC: 46 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.0135 AC: 78 AN: 5766

European-Non Finnish (NFE) AF: 0.000906 AC: 1007 AN: 1111588

Other (OTH) AF: 0.0189 AC: 1144 AN: 60376

GnomAD4 genome AF: 0.0794 AC: 12084 AN: 152210 Hom.: 1562 Cov.: 32 AF XY: 0.0768 AC XY: 5713 AN XY: 74436

African (AFR) AF: 0.275 AC: 11426 AN: 41480

American (AMR) AF: 0.0272 AC: 416 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00548 AC: 19 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.00134 AC: 91 AN: 68004

Other (OTH) AF: 0.0591 AC: 125 AN: 2116

Alfa AF: 0.0234 Hom.: 139

Bravo AF: 0.0902

Asia WGS AF: 0.0190 AC: 68 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Colorectal cancer (1)
-	-	1	Mosaic variegated aneuploidy syndrome 1 (1)
-	-	1	not specified (1)
-	-	1	Premature chromatid separation trait (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.29
DANN	Benign	0.41
PhyloP100		-0.32
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: rs13380241; hg19: chr15-40501993; COSMIC: COSV104598939;