What it does

Filter LoF variants by transcript position and type

Not all candidate LoF variants are created equal. For e.g, a nonsense (stop gain) variant impacting the first 5% of a polypeptide is far more likely to be deleterious than one affecting the last 5%. Assuming you’ve annotated your VCF with snpEff v3.0+, the lof_sieve tool reports the fractional position (e.g. 0.05 for the first 5%) of the mutation in the amino acid sequence. In addition, it also reports the predicted function of the transcript so that one can segregate candidate LoF variants that affect protein_coding transcripts from processed RNA, etc.

Example

Output with default settings:

chrom   start       end        ref  alt  highest_impact  aa_change   var_trans_pos   trans_aa_length var_trans_pct   sample   genotype    gene    transcript       trans_type
chr22   17072346    17072347   C    T    stop_gain       W365*       365             557             0.655296229803  NA19327  C|T         CCT8L2  ENST00000359963  protein_coding
chr22   17072346    17072347   C    T    stop_gain       W365*       365             557             0.655296229803  NA19375  T|C         CCT8L2  ENST00000359963  protein_coding
chr22   17129539    17129540   C    T    splice_donor    None        None            None            None            NA18964  T|C         TPTEP1  ENST00000383140  lincRNA
chr22   17129539    17129540   C    T    splice_donor    None        None            None            None            NA19675  T|C         TPTEP1  ENST00000383140  lincRNA