rs201813238

Variant names:

• chr15-40199694-C-G
• NM_001211.6:c.1368C>G

Your query was ambiguous. Multiple possible variants found:

• chr15-40199694-C-G
• chr15-40199694-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001211.6(BUB1B):​c.1368C>G​(p.Ile456Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: BUB1B NM_001211.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0860

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08431378).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BUB1B	NM_001211.6	c.1368C>G	p.Ile456Met	missense_variant	Exon 10 of 23	ENST00000287598.11	NP_001202.5
LOC107984763	XR_001751506.2	n.218-19493G>C		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BUB1B	ENST00000287598.11	c.1368C>G	p.Ile456Met	missense_variant	Exon 10 of 23	1	NM_001211.6	ENSP00000287598.7
BUB1B	ENST00000412359.7	c.1410C>G	p.Ile470Met	missense_variant	Exon 10 of 23	2		ENSP00000398470.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Dec 31, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The p.I456M variant (also known as c.1368C>G), located in coding exon 10 of the BUB1B gene, results from a C to G substitution at nucleotide position 1368. The isoleucine at codon 456 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.071	T;.
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.60	T;T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.084	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	0.41	N;N
REVEL	Benign	0.055
Sift	Benign	0.26	T;T
Sift4G	Benign	0.19	T;T
Polyphen		0.18	B;B
Vest4		0.19
MutPred		0.094		Loss of ubiquitination at K454 (P = 0.0937);.;
MVP		0.80
MPC		0.24
ClinPred		0.18	T
GERP RS		1.0
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.7
Varity_R		0.031
gMVP		0.11

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-40491895;