Question: Confusing HGVS notation
0
gravatar for MAPK
4.2 years ago by
MAPK1.5k
Washington University in St. Louis
MAPK1.5k wrote:

I have this variant c.828-4A>T (say at chr9:3434923) and I am trying to understand what that actually mean. In VCF format, does it mean this as shown below ?

Chr    start          end          TYPE         REF        ALT
 9    3434923      3434926        indel         AAA         -
hgvs • 1.1k views
ADD COMMENTlink modified 4.2 years ago • written 4.2 years ago by MAPK1.5k
4
gravatar for rbagnall
4.2 years ago by
rbagnall1.6k
Australia
rbagnall1.6k wrote:

It is a single nucleotide substitution (A to T). I wonder if it should be written c.828-4A>T.

When the numbering represents the cDNA sequence and the variant is within an intron, +1 is the first nucleotide of the intron and -1 is the last nucleotide of the intron.

So, your mutation could be an A to T at the fourth last nucleotide of the intron that is spliced out at cDNA position 828.

The HGVS explanation for this type is:

intronic nucleotides (coding DNA reference sequence only)

  • beginning of the intron; the number of the last nucleotide of the preceding exon, a plus sign and the position in the intron, like c.77+1G, c.77+2T, ....

  • end of the intron; the number of the first nucleotide of the following exon, a minus sign and the position upstream in the intron, like ..., c.78-2A, c.78-1G.

  • in the middle of the intron, numbering changes from "c.77+.." to "c.78-.."; for introns with an uneven number of nucleotides the central nucleotide is the last described with a "+" (see Discussion)

  • NOTE: the format c.IVS1+1G and c.IVS1-2G should not be used

ADD COMMENTlink written 4.2 years ago by rbagnall1.6k

@rbagnall Thank you. I have corrected c.828-4A>T

ADD REPLYlink written 4.2 years ago by MAPK1.5k
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