RNA Recommendations

Substitution Variant


Definitions

Substitution
a sequence change where, compared to a reference sequence, one nucleotide is replaced by one other nucleotide.

Description

Format: “prefix”“position_substituted”“reference_nucleotide””>”new_nucleotide”, e.g. r.123a>g

“prefix” = reference sequence used = r.
“position_substituted” = position nucleotide sustituted = 123
“reference_nulceotide” = nucleotide at reference position = a
”>” = type of change is a substitution = >
“new_nucleotide” = substituted nucleotide = g


Note

  • prefix reference sequences accepted are r. (coding and non-coding RNA).
  • changes involving two or more consecutive nucleotides are described as deletion/insertions (indels) (see Deletion/insertion (indel)).
  • nucleotides that have been tested and found not changed are described as r.109u= (see SVD-WG001 (no change)).
  • the description r.76_77delinsuu is preferred over r.[76a>u;77g>u].
    NOTE: by definition this change can not be described as a substitution (like r.76_77ag>uu or r.76ag>uu)
  • it is not correct to describe “polymorphisms” as r.76a/g (see Discussions).

Examples

  • r.76a>c
    a substitution of the “a” nucleotide at r.76 with a “c”
  • r.-14g>c
    a “g” to “c” substitution 14 nucleotides 5’ of the ATG translation initiation codon
  • r.*46u>a
    a “u” to “a” substitution 46 nucleotides 3’ of the translation termination codon
  • r.0
    no RNA from the variant allele could be detected
  • r.spl
    RNA has not been analysed but it is very likely that splicing is affected
  • r.?
    an effect on the RNA level is expected but it is not possible to give a reliable prediction of the consequences (RNA not analysed)
  • the description r.76_77delinsuu is preferred over r.[76a>u;77g>u]
    NOTE: based on the definition of a substitution, i.e. one nucleotide replaced by one other nucleotide, this change can not be described as a substitution like r.76_77ag>uu or r.76ag>uu

Q&A

Are polymorphisms described like r.76a/g?

No, all substitutions are described as r.76a>g. In the past, the format r.76a/g has been used to describe "polymorphic" sequence variants. Note that a description should be neutral, simply describe the change, and not include any other information like predicted or known functional consequences.

Can I describe a GC to TG variant as a dinucleotide substitution (r.4gc>ug)?

No, this is not allowed. By definition a substitution changes one nucleotide into one other nucleotide. The change "ugugcca" to "uguugca" should be described as a deletion/insertion (indel) as r.4_5delinsug.