rs2305653

chr15-40202297-G-A

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BUB1B	NM_001211.6	c.1568-108G>A		intron_variant		ENST00000287598.11
LOC107984763	XR_001751506.2	n.218-22096C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BUB1B	ENST00000287598.11	c.1568-108G>A		intron_variant		1	NM_001211.6	P1
BUB1B	ENST00000412359.7	c.1610-108G>A		intron_variant		2
BUB1B	ENST00000559733.5	c.*481-108G>A		intron_variant, NMD_transcript_variant		3
BUB1B	ENST00000558972.1	n.373-108G>A		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR exome AF: 0.580

Gnomad4 AMR exome AF: 0.522

Gnomad4 ASJ exome AF: 0.401

Gnomad4 EAS exome AF: 0.285

Gnomad4 SAS exome AF: 0.482

Gnomad4 FIN exome AF: 0.557

Gnomad4 NFE exome AF: 0.561

Gnomad4 OTH exome AF: 0.514

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

Gnomad4 AFR AF: 0.582

Gnomad4 AMR AF: 0.508

Gnomad4 ASJ AF: 0.407

Gnomad4 EAS AF: 0.260

Gnomad4 SAS AF: 0.480

Gnomad4 FIN AF: 0.558

Gnomad4 NFE AF: 0.560

Gnomad4 OTH AF: 0.504

Alfa AF: 0.552 Hom.: 4771

Bravo AF: 0.539

Asia WGS AF: 0.373 AC: 1296 AN: 3466

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.60
Dann	Benign	0.49

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: rs2305653; hg19: chr15-40494498;