rs12623473

Positions:

• chr2-110660580-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004336.5(BUB1):​c.1218-544A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00809 in 152,260 control chromosomes in the GnomAD database, including 75 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0081 (75 hom., cov: 32)
• Consequence: BUB1 NM_004336.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.105

Genes affected

BUB1 (HGNC:1148): (BUB1 mitotic checkpoint serine/threonine kinase) This gene encodes a serine/threonine-protein kinase that play a central role in mitosis. The encoded protein functions in part by phosphorylating members of the mitotic checkpoint complex and activating the spindle checkpoint. This protein also plays a role in inhibiting the activation of the anaphase promoting complex/cyclosome. This protein may also function in the DNA damage response. Mutations in this gene have been associated with aneuploidy and several forms of cancer. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BUB1	NM_004336.5	c.1218-544A>G		intron_variant		ENST00000302759.11	NP_004327.1
BUB1	NM_001278616.2	c.1158-544A>G		intron_variant			NP_001265545.1
BUB1	NM_001278617.2	c.1218-544A>G		intron_variant			NP_001265546.1
BUB1	XM_047445616.1	c.1218-544A>G		intron_variant			XP_047301572.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BUB1	ENST00000302759.11	c.1218-544A>G		intron_variant		1	NM_004336.5	ENSP00000302530	P1

Frequencies

GnomAD3 genomes AF: 0.00813 AC: 1237 AN: 152142 Hom.: 77 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.0340

Gnomad FIN AF: 0.00613

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000720

Gnomad OTH AF: 0.00956

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00809 AC: 1232 AN: 152260 Hom.: 75 Cov.: 32 AF XY: 0.00985 AC XY: 733 AN XY: 74446

Gnomad4 AFR AF: 0.000144

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.0115

Gnomad4 EAS AF: 0.168

Gnomad4 SAS AF: 0.0340

Gnomad4 FIN AF: 0.00613

Gnomad4 NFE AF: 0.000720

Gnomad4 OTH AF: 0.00899

Alfa AF: 0.00520 Hom.: 18

Bravo AF: 0.00808

Asia WGS AF: 0.0880 AC: 306 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.2
DANN	Benign	0.73

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: rs12623473; hg19: chr2-111418157;