rs61733369

chr15-40196716-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS1

The NM_001211.6(BUB1B):c.1230C>T(p.Phe410=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000147 in 1,614,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00089 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000070 (0 hom.)
• Consequence: BUB1B NM_001211.6 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.17

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP6: Variant 15-40196716-C-T is Benign according to our data. Variant chr15-40196716-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 412525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.17 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000887 (135/152242) while in subpopulation AFR AF= 0.00289 (120/41542). AF 95% confidence interval is 0.00247. There are 0 homozygotes in gnomad4. There are 67 alleles in male gnomad4 subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BUB1B	NM_001211.6	c.1230C>T	p.Phe410=	synonymous_variant	9/23	ENST00000287598.11
LOC107984763	XR_001751506.2	n.218-16515G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BUB1B	ENST00000287598.11	c.1230C>T	p.Phe410=	synonymous_variant	9/23	1	NM_001211.6	P1

Frequencies

GnomAD3 genomes AF: 0.000887 AC: 135 AN: 152124 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.000231 AC: 58 AN: 251340 Hom.: 0 AF XY: 0.000213 AC XY: 29 AN XY: 135860

Gnomad AFR exome AF: 0.00302

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.0000705 AC: 103 AN: 1461760 Hom.: 0 Cov.: 32 AF XY: 0.0000646 AC XY: 47 AN XY: 727172

Gnomad4 AFR exome AF: 0.00236

Gnomad4 AMR exome AF: 0.000134

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000719

Gnomad4 OTH exome AF: 0.000132

GnomAD4 genome AF: 0.000887 AC: 135 AN: 152242 Hom.: 0 Cov.: 32 AF XY: 0.000900 AC XY: 67 AN XY: 74440

Gnomad4 AFR AF: 0.00289

Gnomad4 AMR AF: 0.000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.000560 Hom.: 0

Bravo AF: 0.000967

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Inborn genetic diseases Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 15, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Colorectal cancer Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Mosaic variegated aneuploidy syndrome 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 06, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
Cadd	Benign	9.3
Dann	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs61733369; hg19: chr15-40488917;