Ambiguous allele (UIPAC) not properly handled according to VCF specs 4.3

[huguesfontenelle]

The Human Decoy Sequences (hs37d5) prepared according to [README]
contains ambiguous IUPAC references.
In particular it has some S (C or G).

The VCF 4.3 specs prescribe that a caller outputs the first base, but not the IUPAC ambiguous base:

REF - reference base(s): Each base must be one of A,C,G,T,N (case insensitive).
[...]
If the reference sequence contains IUPAC ambiguity codes not allowed by this specification (such as R = A/G), the ambiguous reference base must be reduced to a concrete base by using the one that is first alphabetically (thus R as a reference base is converted to A in VCF.)

For example, I should not be seeing a call such as:

hs37d5  33184489        .       S       C       .       PASS    DP=33;SS=1;SSC=0;GPV=1.3852e-19;SPV=1   GT:GQ:DP:RD:AD:FREQ:DP4 1/1:.:10:0:10:100%:0,0,9,1 1/1:.:23:0:23:100%:0,0,23,0

Here the S should have been interpreted as C. Therefore there should have been no call.

This bug causes false positives and, more importantly, causes downstream tools to fail, such as igvtools

[NevenaaNikolic]

I am experiencing the same issue. How to overcome this problem, is it going to be fixed at some time in the future?

[myourshaw]

Just weighing in as another guy bit by the same dog (VarScan2). Errors were encountered in Picard FixVcfHeader, which I have to use to fix other non-compliant VarScan2-generated VCFs.

Exception in thread "main" htsjdk.tribble.TribbleException: The provided VCF file is malformed at approximately line number 161245: unparsable vcf record with allele R, for input source: file:///home/dnanexus/inputs/input4444483750468838029/LRF2-10_ST@1212020JH_ST.b37.map.dedup.sample.varscan2.fpfilter.fail.add_contigs.vcf

Exception in thread "main" htsjdk.tribble.TribbleException: The provided VCF file is malformed at approximately line number 128832: unparsable vcf record with allele Y, for input source: file:///home/dnanexus/inputs/input1153832023365751001/MP17-00247-NT_K@03102020JH_ST.b37.map.dedup.sample.varscan2.fpfilter.fail.add_contigs.vcf

Exception in thread "main" htsjdk.tribble.TribbleException: The provided VCF file is malformed at approximately line number 101179: unparsable vcf record with allele S, for input source: file:///home/dnanexus/inputs/input8947911205436031285/MG18-2516@10212020JH_ST.b37.map.dedup.sample.varscan2.fpfilter.fail.add_contigs.vcf