rs368869250
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP5BS1_Supporting
The ENST00000287598.11(BUB1B):c.179+5G>A variant causes a splice donor 5th base, intron change. The variant allele was found at a frequency of 0.0000297 in 1,614,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
ENST00000287598.11 splice_donor_5th_base, intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BUB1B | NM_001211.6 | c.179+5G>A | splice_donor_5th_base_variant, intron_variant | ENST00000287598.11 | NP_001202.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BUB1B | ENST00000287598.11 | c.179+5G>A | splice_donor_5th_base_variant, intron_variant | 1 | NM_001211.6 | ENSP00000287598 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000171 AC: 26AN: 152214Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251460Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135902
GnomAD4 exome AF: 0.0000150 AC: 22AN: 1461866Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 727234
GnomAD4 genome AF: 0.000171 AC: 26AN: 152214Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74372
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Aug 17, 2023 | Intronic +5 splice site variant in a gene for which loss of function is a known mechanism of disease, and both splice predictors and evolutionary conservation support a deleterious effect, although in the absence of functional evidence the actual effect of this sequence change is unknown.; Has not been previously published as pathogenic or benign to our knowledge - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 23, 2022 | The c.179+5G>A intronic alteration consists of a G to A substitution nucleotides after coding exon 2 in the BUB1B gene. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Mosaic variegated aneuploidy syndrome 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 27, 2023 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 533913). This variant has not been reported in the literature in individuals affected with BUB1B-related conditions. This variant is present in population databases (rs368869250, gnomAD 0.05%). This sequence change falls in intron 2 of the BUB1B gene. It does not directly change the encoded amino acid sequence of the BUB1B protein. It affects a nucleotide within the consensus splice site. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at