Hello,

I have a question about sequence conflicts that occasionally show up between 
dbSNP missense SNP annotation page and refrence seqeunce. Here is one example 
from hg19 / dbSNP 131 SNP annotation page:

dbSNP build 131 rs72894038

dbSNP: rs72894038
Position: chr1:1141765-1141765
Band: 1p36.33
Genomic Size: 1

<skipped>

Coding annotations by dbSNP:
NM_004195: missense G (GGC) --> S (AGC)
NM_148901: missense G (GGC) --> S (AGC)
NM_148902: missense G (GGC) --> S (AGC)

UCSC's predicted function relative to selected gene tracks:
UCSC Genes      TNFRSF18 (uc001add.2)   missense G (GGG) --> R (AGG)
UCSC Genes      TNFRSF18 (uc001adc.2)   missense G (GGG) --> R (AGG)
UCSC Genes      TNFRSF18 (uc001adb.2)   missense G (GGG) --> R (AGG)

Now if you look at the sequence of uc001add.2 transcript, this position in 
fact falls withing codon GGC (NOT GGG) on the reference sequence. It is a bit 
complicated by the fact that this transcript is annotated on minus strand and 
the codon in question is split between the end of exon 1 and start of exon 2:

Exon 1:
ATG GCA CAG CAC GGG GCG ATG GGC GCG TTT CGG
GCC CTG TGC GGC CTG GCG CTG CTG TGC GCG CTC
AGC CTG GGT CAG CGC CCC ACC GGG GGT CCC GGG
TGC GGC CCT GGG CGC CTC CTG CTT GGG ACG GGA
ACG GAC GCG CGC TGC TGC CGG GTT CAC ACG ACG
CGC TGC TGC CGC GAT TAC CCG G

Exon 2:
 GC GAG GAG TGC TGT TCC GAG TGG GAC TGC ATG
<rest skipped>

I have used Genomic Sequence link on the gene annotation page of Genome 
Browser to extract the above exon sequences but I obtain the same results when 
using exons/CDS annotations from MySQL knownGene table for this transcript and 
fetching corresponding sequences from reference chromosome assemblies. I have 
also verified this using hg19 Genome Browser web interface. In all cases I can 
see GGC codon, not GGG. Note, that the codon sequence in NCBI annotations is 
correct.

This is not an isolated (although rare) case and I can supply more examples if 
necessary. Since there is no explananiton on how exactly this "UCSC's 
predicted function relative to selected gene tracks" section of the SNP 
annotation page is produced, I wonder what may have caused such descrepancies?

Best,
Ivan



-- 
Ivan Adzhubey, Ph.D.
Instructor
Division of Genetics, Dept of Medicine
Brigham & Women's Hospital, Harvard Medical School
HMS New Research Building, Room 0464C
77 Avenue Louis Pasteur
Boston, MA 02115
tel.: (617) 525-4728
fax:  (617) 525-4705
web: http://genetics.bwh.harvard.edu/genetics/members/Ivan_Adzhubey.html
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