15-40202608-C-T
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PP5_Moderate
The NM_001211.6(BUB1B):c.1648C>T(p.Arg550Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,952 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. R550R) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001211.6 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BUB1B | NM_001211.6 | c.1648C>T | p.Arg550Ter | stop_gained | 14/23 | ENST00000287598.11 | |
LOC107984763 | XR_001751506.2 | n.218-22407G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BUB1B | ENST00000287598.11 | c.1648C>T | p.Arg550Ter | stop_gained | 14/23 | 1 | NM_001211.6 | P1 | |
BUB1B | ENST00000412359.7 | c.1690C>T | p.Arg564Ter | stop_gained | 14/23 | 2 | |||
BUB1B | ENST00000558972.1 | n.453C>T | non_coding_transcript_exon_variant | 4/5 | 3 | ||||
BUB1B | ENST00000559733.5 | c.*561C>T | 3_prime_UTR_variant, NMD_transcript_variant | 7/7 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152116Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251470Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135912
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461836Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727226
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152116Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74302
ClinVar
Submissions by phenotype
Mosaic variegated aneuploidy syndrome 1 Pathogenic:2
Pathogenic, no assertion criteria provided | research | Donald Williams Parsons Laboratory, Baylor College of Medicine | Apr 30, 2014 | This nonsense variant is categorized as deleterious according to ACMG guidelines (PMID:18414213). It would be pathogenic in a recessive state; heterozygotes would be carriers for the condition. It was found once in our study heterozygous, maternally inherited in a 7-year-old male with glioma; LOH was not detected in the tumor in this region. There was a paternal family history of cancer. - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 23, 2022 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 438799). This premature translational stop signal has been observed in individual(s) with mosaic variegated aneuploidy (PMID: 28976722). This variant is present in population databases (rs767213728, gnomAD 0.007%). This sequence change creates a premature translational stop signal (p.Arg550*) in the BUB1B gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BUB1B are known to be pathogenic (PMID: 15475955, 21190457). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at