Name this alternative INDEL format

Question

I have recently been working with variants which are represented in a non-standard format. This alternative format uses a period instead of prefixing variants with a reference base. What is this format called?

There is no specific output format associated with it. It's part of some calling code I've inherited. I figured that this existed elsewhere. But, I could be wrong.

Expected Format:

Insertion:

pos=4
alt=ATTT
ref=A

Deletion:

pos=4
alt=A
ref=ATTT

Alternative Format:

Insertion:

pos=5
alt=TTT
ref=.

Deletion:

pos=5
alt=.
ref=TTT

Answer 1

The alternative deletion representation that you are describing, i.e. using . to represent alternate alleles that are not present, is allowed within the definition of the VCF format (in other words, this representation can be found in a standard format). An example of this is provided on the Wikipedia page for VCF:

#CHROM POS      ID         REF   ALT    QUAL  FILTER
20     1230237  .          T     .      47    PASS

While missing values are allowed for ALT, they are not typically used because they lead to ambiguous variant definitions.

For missing REF values, the VCF format specification has the following explanation:

Each base must be one of A,C,G,T,N (case insensitive). Multiple bases are permitted. The value in the POS field refers to the position of the first base in the String. For simple insertions and deletions in which either the REF or one of the ALT alleles would otherwise be null/empty, the REF and ALT Strings must include the base before the event (which must be reflected in the POS field), unless the event occurs at position 1 on the contig in which case it must include the base after the event....

To work around this ambiguity, VCF files are commonly left-normalised so that the specified sequences and variants can be precisely placed within the reference genome. Left normalisation can be carried out using bcftools norm.

More details on left normalisation can be found here:

https://genome.sph.umich.edu/wiki/Variant_Normalization#Left_alignment

• A variant is normalized if and only if it is parsimonious and left aligned.
• A variant is parsimonious if and only if it is represented in as few nucleotides as possible without an allele of length 0.
• A variant is left aligned if and only if it is no longer possible to shift its position to the left while keeping the length of all its alleles constant.

In other words, these are non-parsimonious variants.