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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
all variants should be described at the DNA level, descriptions at the RNA and/or protein level may be given in addition
prefix reference sequences accepted are r. (coding and non-coding RNA).
substitutions involving two or more consecutive nucleotides are described as deletion/insertions (indels) (see Deletion/insertion (delins)).
two substitutions separated by one or more nucleotides should be described individually and not as a “delins”
exception: two variants separated by one nucleotide, together affecting one amino acid, should be described as a “delins” (e.g. r.142_144delinsugg (p.Arg48Trp)).
NOTE: this prevents tools predicting the consequences of a variant to make conflicting and incorrect predictions of two different substitutions at one position
nucleotides that have been tested and found not changed are described as r.109u=, r.4567_4569= (see SVD-WG001 (no change)).
it is not correct to describe “polymorphisms” as r.76a/g (see Discussions).
Examples
NM_004006.3:r.76a>c
a substitution of the “a” nucleotide at r.76 with a “c”
NM_004006.3:r.76_77delinsug
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_77aa>ug or r.76aa>ug
NM_004006.3:r.(1388g>a)
the predicted consequences at RNA level is a substitution of the “g” nucleotide at r.1388 with a “g”
NM_004006.3:r.123=
a screen was performed showing that nucleotide r.123 was a “c” as in the coding DNA reference sequence (the nucleotide was not changed).
NM_004006.1:r.-14a>c
a “a” to “c” substitution 14 nucleotides 5’ of the ATG translation initiation codon
NM_004006.3:r.*41u>a
a “u” to “a” substitution 41 nucleotides 3’ of the translation termination codon
NM_004006.3:r.[897u>g,832_960del]
two different transcripts, 897u>g and r.832_960del, derive from one variant (NM_004006.3:c.897T>G at the DNA level)
NOTE: for more examples of variants affecting splicing see RNA splicing
NM_004006.1:r.0
no RNA from the variant allele could be detected
NM_004006.3:r.spl
RNA has not been analysed but it is very likely that splicing is affected
NM_004006.3: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)
NM_004006.3:r.85=/u>c
a mosaic case where at position 85 besides the normal sequence (a U, described as “=”) also transcripts are found containing a C (r.85u>c)
NOTE: irrespective of the frequency in which each nucleotide was found, the reference is always described first
NM_004006.3:r.85=//u>c
a chimeric case, i.e. the sample is a mix of cells containing r.85= and r.85u>c.
NOTE: irrespective of the frequency in which each nucleotide was found, the reference is always described first
Q&A
When I only sequenced RNA (cDNA) and not genomic DNA should I then give the description of a variant at DNA level in parenthesis?
Yes, while the variant at RNA level can be described as r.76a>g on DNA level, based on a coding DNA reference, sequence it should be described as c.(76A>G).
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.
I found a variant on DNA level which is a well-characterised splice variant. Is it correct to describe the variant as concluded from literature?
No, you should report what you have found. You can however use the published data to give the predicted consequences on RNA/protein level, e.g. NM_004006.3:c.3430C>T r.(3277_3432del) p.(Leu1093_Gln1144del).