Reference is deletion and negative genomic position label

Question

[Shicheng Guo]

I found an interesting thing. rs71587061 is a insertion which means, in the reference genomic, It is a deletion, then how to descriptive the genomic position for this SNP?

dbSNP build 150 rs71587061
dbSNP: rs71587061
Position: chr1:45194431-45194430
Band: 1p34.1
Genomic Size: 0
Strand: +
Observed: -/C
Reference allele:   -

https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=71587061

hg19 not hg38

reference ≠ major ≠ ancestral ≠ wildtype

[cpad0112]

querying b151 dbsnp vcf didn't yield any results.

 $ tabix ftp://ftp.ncbi.nih.gov/snp/organisms/human_9606_b151_GRCh38p7/VCF/All_20180418.vcf.gz 1:45194429-45194431

[Shicheng Guo]

for GRCh38

 $ tabix ftp://ftp.ncbi.nih.gov/snp/organisms/human_9606_b151_GRCh38p7/VCF/All_20180418.vcf.gz 1:44728758-44728759

Answer 1

[Kevin Blighe]

Hey dude,

No, it's not a deletion in the 'typical' reference genomes used by the Genome Reference Consortium (GRC). This is an insertion variant that was identified in John Craig Venter's genome. It's not even listed in 1000 Genomes Phase III data. It's validation status is not listed on dbSNP. It may never have even been validated in Venter's actual genomic DNA and could be a sequencing error.

However, as Venter's genome is also regarded as a reference genome itself, you could make the argument that —yes indeed— it is a deletion in the GRC human (GRCh) builds. Switching the context around and regarding the GRCh builds as the references, this variant would then appear as an insertion in Venter's genome.

A problem that we have in comparative genomics is that the reference genomes prior to hg38 / GRCh38 were mostly based on the genomes of single individuals, including that of hg19 / GRCh37 (~70% of it was from some donor from Buffalo, New York, USA). So, weird situations like this variant's can arise, and also weird things like this: A: Alternate nucleotide is more frequent than reference nucleotide. OMG I'm dizzy.

Kevin

Answer 2

[Ram]

It's an insertion. If you see the HGVS notation, it's NC_000001.10:g.45194430_45194431insC. The annotation source you got it from got their notations wrong.