15-40161179-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001211.6(BUB1B):c.-42A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0122 in 1,609,880 control chromosomes in the GnomAD database, including 168 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.010 (14 hom., cov: 32)
  • Exomes 𝑓: 0.012 (154 hom.)
• Consequence: BUB1B NM_001211.6 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.156

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 15-40161179-A-G is Benign according to our data. Variant chr15-40161179-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1211774.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0102 (1552/152254) while in subpopulation NFE AF= 0.0142 (968/68012). AF 95% confidence interval is 0.0135. There are 14 homozygotes in gnomad4. There are 784 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 14 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BUB1B	NM_001211.6	c.-42A>G		5_prime_UTR_variant	1/23	ENST00000287598.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BUB1B	ENST00000287598.11	c.-42A>G		5_prime_UTR_variant	1/23	1	NM_001211.6	P1

Frequencies

GnomAD3 genomes AF: 0.0102 AC: 1552 AN: 152136 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.00210

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00628

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.0348

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0142

Gnomad OTH AF: 0.00623

GnomAD3 exomes AF: 0.00999 AC: 2420 AN: 242150 Hom.: 17 AF XY: 0.00965 AC XY: 1266 AN XY: 131198

Gnomad AFR exome AF: 0.00194

Gnomad AMR exome AF: 0.00292

Gnomad ASJ exome AF: 0.00355

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000608

Gnomad FIN exome AF: 0.0352

Gnomad NFE exome AF: 0.0135

Gnomad OTH exome AF: 0.00829

GnomAD4 exome AF: 0.0124 AC: 18140 AN: 1457626 Hom.: 154 Cov.: 31 AF XY: 0.0122 AC XY: 8820 AN XY: 724724

Gnomad4 AFR exome AF: 0.00171

Gnomad4 AMR exome AF: 0.00384

Gnomad4 ASJ exome AF: 0.00434

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000680

Gnomad4 FIN exome AF: 0.0352

Gnomad4 NFE exome AF: 0.0137

Gnomad4 OTH exome AF: 0.0110

GnomAD4 genome AF: 0.0102 AC: 1552 AN: 152254 Hom.: 14 Cov.: 32 AF XY: 0.0105 AC XY: 784 AN XY: 74442

Gnomad4 AFR AF: 0.00209

Gnomad4 AMR AF: 0.00627

Gnomad4 ASJ AF: 0.00403

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.0348

Gnomad4 NFE AF: 0.0142

Gnomad4 OTH AF: 0.00616

Alfa AF: 0.0125 Hom.: 4

Bravo AF: 0.00770

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 24, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	8.6
Dann	Benign	0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs183777343; hg19: chr15-40453380; COSMIC: COSV55014982;