Types

Variant Type(s) are used to classify variants by Sequence Ontology terms.

Variant Types permit advanced searching for categories of variants in the CIViC interface and downstream semantic analyses of CIViC variants. Some examples of variant types are listed below.

Curating Variant Types

The most specific term(s) that can be applied to a given variant should be utilized. Use of the Sequence Ontology browser is recommended to identify appropriate terms.

When choosing variant types, selection of multiple terms is supported in order to capture both functional and structural effects of the variant. However, these terms should not be ancestors or descendents of one another, and all selected terms should be descendents of the ‘sequence_variant’ term whenever possible.

Variant Type Guidelines

  • Choose the most specific terms.

  • Do not use terms that are ancestors/decendants of each other.

  • Wherever possible use the ‘sequence_variant’ tree of the sequence ontology.

Curation Guidelines for Specific Sequence Ontology Types

Sequence Ontology Term

Sequence Ontology Definition

Comments

missense_variant

A sequence variant, that changes one or more bases, resulting in a different amino acid sequence but where the length is preserved.

stop_gained

A sequence variant whereby at least one base of a codon is changed, resulting in a premature stop codon, leading to a shortened polypeptide.

Also known as a nonsense variant.

protein_altering_variant

A sequence_variant which is predicted to change the protein encoded in the coding sequence.

frameshift_truncation

A frameshift variant that causes the translational reading frame to be shortened relative to the reference feature.

inframe_deletion

An inframe non synonymous variant that deletes bases from the coding sequence.

inframe_insertion

An inframe non synonymous variant that inserts bases into in the coding sequence.

[ gene_variant

OR

transcript_variant ]

AND

[ loss_of_function_variant

OR

gain_of_function_variant ]

[ gene_variant: A sequence variant where the structure of the gene is changed.

OR

transcript_variant: A sequence variant that changes the structure of the transcript ]

AND

[ loss_of_function_variant: A sequence variant whereby the gene product has diminished or abolished function.

OR

gain_of_function_variant: A sequence variant whereby new or enhanced function is conferred on the gene product. ]

Depends on situation.

exon_variant

A sequence variant that changes exon sequence.

transcript_fusion

OR RARELY…

gene_fusion

transcript_fusion: A feature fusion where the deletion brings together transcript regions.

OR

gene_fusion: A sequence variant whereby a two genes have become joined.

Depends on situation.

Note that transcript_fusion mentions “deletion” specifically as the genomic alteration, and both gene_fusion and transcript_fusion are children of feature_fusion, which also mentions “deletion” specifically. However, it is assumed that deletion is just one possible mechanism (along with translocation, inversion, etc) for bringing two gene or transcribed regions together. The decision of which term to use therefore rests on the level of specificity. If the genomic event is thought to result in a fusion transcript then “transcript_fusion” is the preferred term.

transcript_fusion

AND

missense_variant

transcript_fusion: A feature fusion where the deletion brings together transcript regions.

AND

missense_variant: A sequence variant that changes one or more bases, resulting in a different amino acid sequence but where the length is preserved.

transcript_translocation

OR

feature_translocation

OR

transcript_fusion

transcript_translocation: A feature translocation where the region contains a transcript.

OR

feature_translocation: A sequence variant, caused by an alteration of the genomic sequence, where the structural change, a translocation, is greater than the extent of the underlying genomic features.

OR

transcript_fusion: A feature fusion where the deletion brings together transcript regions.

Depends on situation.

wild_type

An attribute describing sequence with the genotype found in nature and/or standard laboratory stock.

loss_of_heterozygosity

A functional variant whereby the sequence alteration causes a loss of function of one allele of a gene.

transcript_amplification

A feature amplification of a region containing a transcript.

transcript_ablation

A feature ablation whereby the deleted region includes a transcript feature.

copy_number_change

A sequence variant where copies of a feature (CNV) are either increased or decreased.

loss_of_function_variant

A sequence variant whereby the gene product has diminished or abolished function.

loss_of_function_variant…?

transcript_ablation…?

loss_of_fuction_variant: A sequence variant whereby the gene product has diminished or abolished function.

transcript_ablation: A feature ablation whereby the deleted region includes a transcript feature.

Depends on situation.

exon_loss_variant

A sequence variant whereby an exon is lost from the transcript.

5_prime_UTR_variant

A UTR variant of the 5’ UTR.

3_prime_UTR_variant

A UTR variant of the 3’ UTR.

N/A

The Sequence Ontology does not currently describe expression or epigenetic variants.

Variant Type Examples

Sequence Ontology Term

Examples

missense_variant

G12D

stop_gained

R130*

protein_altering_variant

G12

KINASE DOMAIN MUTATION

frameshift_truncation

V2288fs*1

inframe_deletion

DEL I843

V560DEL

DEL 755-759

inframe_insertion

P780INS

M774INSAYVM

ITD

[ gene_variant

OR

transcript_variant ]

AND

[ loss_of_function_variant

OR

gain_of_function_variant ]

MUTATION

exon_variant

EXON 10 MUTATION

transcript_fusion

OR RARELY…

gene_fusion

EML4-ALK

ALK FUSIONS

transcript_fusion

AND

missense_variant

EML4-ALK G1269A

transcript_translocation

OR

feature_translocation

OR

transcript_fusion

REARRANGEMENT

wild_type

WILD TYPE

loss_of_heterozygosity

LOH

transcript_amplification

AMPLIFICATION

transcript_ablation

DELETION

copy_number_change

COPY NUMBER VARIATION

loss_of_function_variant

LOSS-OF-FUNCTION

loss_of_function_variant…?

transcript_ablation…?

LOSS

exon_loss_variant

EXON 14 SKIPPING MUTATION

5_prime_UTR_variant

5’ UTR MUTATION

3_prime_UTR_variant

3’ UTR MUTATION

N/A

EXPRESSION

NUCLEAR EXPRESSION

CYTOPLASMIC EXPRESSION

OVEREXPRESSION

UNDEREXPRESSION

METHYLATION

PROMOTER METHYLATION

PROMOTER HYPERMETHYLATION