rs11630664

Variant names:

• chr15-40208785-C-T
• rs11630664
• NM_001211.6:c.2143+15C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-40208785-C-T
• chr15-40208785-C-A
• chr15-40208785-C-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.2143+15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 1,599,102 control chromosomes in the GnomAD database, including 226,339 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (17323 hom., cov: 31)
  • Exomes 𝑓: 0.53 (209016 hom.)
• Consequence: BUB1B NM_001211.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.522
• Publications: 6 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=-0.83).
• BP6: Variant 15-40208785-C-T is Benign according to our data. Variant chr15-40208785-C-T is described in ClinVar as Benign. ClinVar VariationId is 257634.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.554 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.2143+15C>T		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.2143+15C>T		intron	N/A	ENSP00000287598.7	O60566-1
	BUB1B	ENST00000412359.7	TSL:2	c.2185+15C>T		intron	N/A	ENSP00000398470.3	O60566-3
	BUB1B	ENST00000918306.1		c.2245+15C>T		intron	N/A	ENSP00000588365.1

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70222 AN: 151798 Hom.: 17310 Cov.: 31

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.636

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.441

GnomAD2 exomes AF: 0.493 AC: 123325 AN: 250390 AF XY: 0.497

Gnomad AFR exome AF: 0.298

Gnomad AMR exome AF: 0.506

Gnomad ASJ exome AF: 0.401

Gnomad EAS exome AF: 0.248

Gnomad FIN exome AF: 0.558

Gnomad NFE exome AF: 0.556

Gnomad OTH exome AF: 0.489

GnomAD4 exome AF: 0.533 AC: 770770 AN: 1447184 Hom.: 209016 Cov.: 33 AF XY: 0.533 AC XY: 383961 AN XY: 720986

African (AFR) AF: 0.294 AC: 9775 AN: 33246

American (AMR) AF: 0.507 AC: 22658 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 10292 AN: 26068

East Asian (EAS) AF: 0.282 AC: 11160 AN: 39630

South Asian (SAS) AF: 0.481 AC: 41327 AN: 85946

European-Finnish (FIN) AF: 0.558 AC: 29363 AN: 52648

Middle Eastern (MID) AF: 0.406 AC: 2329 AN: 5734

European-Non Finnish (NFE) AF: 0.559 AC: 614321 AN: 1099280

Other (OTH) AF: 0.493 AC: 29545 AN: 59938

GnomAD4 genome AF: 0.463 AC: 70267 AN: 151918 Hom.: 17323 Cov.: 31 AF XY: 0.461 AC XY: 34243 AN XY: 74220

African (AFR) AF: 0.301 AC: 12456 AN: 41446

American (AMR) AF: 0.480 AC: 7334 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 1392 AN: 3470

East Asian (EAS) AF: 0.259 AC: 1332 AN: 5150

South Asian (SAS) AF: 0.479 AC: 2302 AN: 4808

European-Finnish (FIN) AF: 0.557 AC: 5859 AN: 10516

Middle Eastern (MID) AF: 0.431 AC: 125 AN: 290

European-Non Finnish (NFE) AF: 0.559 AC: 37950 AN: 67944

Other (OTH) AF: 0.444 AC: 938 AN: 2114

Alfa AF: 0.386 Hom.: 3339

Bravo AF: 0.447

Asia WGS AF: 0.356 AC: 1238 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.5
DANN	Benign	0.30
PhyloP100		-0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs11630664; hg19: chr15-40500986; COSMIC: COSV55016029; COSMIC: COSV55016029;