rs2305653

Variant names:

• chr15-40202297-G-A
• rs2305653
• NM_001211.6:c.1568-108G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001211.6(BUB1B):​c.1568-108G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 929,006 control chromosomes in the GnomAD database, including 135,885 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.54 (22827 hom., cov: 30)
  • Exomes 𝑓: 0.53 (113058 hom.)
• Consequence: BUB1B NM_001211.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.28
• 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: 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

LOC107984763 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 15-40202297-G-A is Benign according to our data. Variant chr15-40202297-G-A is described in ClinVar as Benign. ClinVar VariationId is 1276830.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.576 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.1568-108G>A		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.1568-108G>A		intron	N/A	ENSP00000287598.7
	BUB1B	ENST00000412359.7	TSL:2	c.1610-108G>A		intron	N/A	ENSP00000398470.3
	BUB1B	ENST00000558972.1	TSL:3	n.373-108G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82418 AN: 151612 Hom.: 22793 Cov.: 30

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.636

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.558

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.502

GnomAD4 exome AF: 0.534 AC: 415061 AN: 777278 Hom.: 113058 AF XY: 0.533 AC XY: 217224 AN XY: 407510

African (AFR) AF: 0.580 AC: 10599 AN: 18282

American (AMR) AF: 0.522 AC: 13296 AN: 25454

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 7814 AN: 19494

East Asian (EAS) AF: 0.285 AC: 10186 AN: 35682

South Asian (SAS) AF: 0.482 AC: 30136 AN: 62514

European-Finnish (FIN) AF: 0.557 AC: 26053 AN: 46738

Middle Eastern (MID) AF: 0.433 AC: 1170 AN: 2700

European-Non Finnish (NFE) AF: 0.561 AC: 296758 AN: 529346

Other (OTH) AF: 0.514 AC: 19049 AN: 37068

GnomAD4 genome AF: 0.544 AC: 82510 AN: 151728 Hom.: 22827 Cov.: 30 AF XY: 0.540 AC XY: 40056 AN XY: 74144

African (AFR) AF: 0.582 AC: 24053 AN: 41328

American (AMR) AF: 0.508 AC: 7752 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1409 AN: 3466

East Asian (EAS) AF: 0.260 AC: 1339 AN: 5146

South Asian (SAS) AF: 0.480 AC: 2308 AN: 4810

European-Finnish (FIN) AF: 0.558 AC: 5869 AN: 10514

Middle Eastern (MID) AF: 0.452 AC: 131 AN: 290

European-Non Finnish (NFE) AF: 0.560 AC: 38006 AN: 67904

Other (OTH) AF: 0.504 AC: 1063 AN: 2110

Alfa AF: 0.553 Hom.: 4896

Bravo AF: 0.539

Asia WGS AF: 0.373 AC: 1296 AN: 3466

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.60
DANN	Benign	0.49
PhyloP100		-1.3
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: rs2305653; hg19: chr15-40494498;