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.
splice_acceptor_variant	A variant the impacts the RNA splice acceptor site (i.e. at or upstream/3prime of an exon edge)
splice_donor_variant	A variant the impacts the RNA donor acceptor site (i.e. at or downstream/5prime of an exon edge)
[ 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.
synonymous_variant	A sequence variant where there is no resulting change to the encoded amino acid.
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