Question: Inverted base and amino acid change in Annovar
0
gravatar for user31888
2.7 years ago by
user3188880
United States
user3188880 wrote:

I detected the following variant and annotated it with Annovar (using hg19 ref. genome):

Chr: 17
Start: 7579472
Ref.: G
Alt: C
dbSNP: rs1042522
AAChange.ensGene: ENSG00000141510:ENST00000359597:exon3:c.C215G:p.P72R

The AAChange fits with the dbSNP entry (both C>G and Pro>Arg), but differs with my Ref. and Alt (they are inverted). Also when I load my ref. genome into IGV, the position falls into a CGG codon that codes for Arg. Replacing the G by C produces a CGC codon that also codes for a Arg, not a Pro.

Why the annotation is inverted compared to my Ref./Alt.?

* EDIT *

Wildtype:
sense       CGG
              ^
antisense   GCC     ==>     Pro

Mutant:
sense       CGC
              ^
antisense   GCG     ==>     Ala

(the "^" indicates the mutation position on the sense strand, i.e. 17:7579472)
annovar • 901 views
ADD COMMENTlink modified 2.7 years ago • written 2.7 years ago by user3188880
0
gravatar for harold.smith.tarheel
2.7 years ago by
United States
harold.smith.tarheel4.5k wrote:

You're looking on the wrong strand. This gene is in the antisense orientation on the reference. The reference codon is actually 'CCG' (Pro), and the SNP is 'CGG' (Arg).

ADD COMMENTlink written 2.7 years ago by harold.smith.tarheel4.5k

Harold, it makes sense for the codon encoding Pro but not for the mutant that would code for Ala in this case (see edit on the OP). I am clearly missing something...

ADD REPLYlink modified 2.7 years ago • written 2.7 years ago by user3188880

LMGTFY: dbSNP rs=1042522

ADD REPLYlink written 2.7 years ago by harold.smith.tarheel4.5k

I saw that. Does not answer the question

ADD REPLYlink written 2.7 years ago by user3188880

Actually, it does. The SNP is in the second nucleotide of the codon, not the third as your edit indicates. Your positioning may be off due to zero-based vs one-based counting.

ADD REPLYlink written 2.7 years ago by harold.smith.tarheel4.5k
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