chr15-40208657-G-T

Position:

• chr15-40208657-G-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.2030G>T​(p.Arg677Leu) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BUB1B NM_001211.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05

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=0.091140896).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BUB1B	NM_001211.6	c.2030G>T	p.Arg677Leu	missense_variant	16/23	ENST00000287598.11	NP_001202.5
LOC107984763	XR_001751506.2	n.218-28456C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BUB1B	ENST00000287598.11	c.2030G>T	p.Arg677Leu	missense_variant	16/23	1	NM_001211.6	ENSP00000287598	P1
BUB1B	ENST00000412359.7	c.2072G>T	p.Arg691Leu	missense_variant	16/23	2		ENSP00000398470

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.18	T;.
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.70	T;T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.091	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.69	N;.
MutationTaster	Benign	0.98	N;N
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.015
Sift	Benign	0.24	T;T
Sift4G	Benign	0.29	T;T
Polyphen		0.0	B;.
Vest4		0.069
MutPred		0.32		Loss of solvent accessibility (P = 0.0022);.;
MVP		0.64
MPC		0.25
ClinPred		0.076	T
GERP RS		1.6
Varity_R		0.047
gMVP		0.30

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

LitVar

Other links and lift over

dbSNP: rs557521971; hg19: chr15-40500858;