How to differentiate these sequence name and changes

Question

[Nawaj Shaikh]

Can anybody guide me in details on the following data set,

1.What is difference between Sequence name mentioned below (e.g. GRCh37.p13 chr3 and TLR9 RefSeqGene etc)

1. What is difference between Change mentioned below (NC_000003.11:g.52256697C>T andNG_033933.1:g.8483G>T and NG_033933.1:g.8483G>A )

2. Difference between them, how it affect on decision of SNP findings?

   Genomic Placements Sequence name Change

   GRCh37.p13 chr 3 NC_000003.11:g.52256697C>T GRCh37.p13 chr 3 NC_000003.11:g.52256697C>A GRCh38.p7 chr 3 NC_000003.12:g.52222681C>T GRCh38.p7 chr 3 NC_000003.12:g.52222681C>A TLR9 RefSeqGene NG_033933.1:g.8483G>A TLR9 RefSeqGene NG_033933.1:g.8483G>T

   Gene: TLR9, toll like receptor 9 (minus strand) Molecule type Change Codon/Amino acid SO Term TLR9 transcript NM_017442.3:c.1635G>T CCG>CCT Coding Sequence Variant toll-like receptor 9 precursor NP_059138.1:p.Pro545= P[Pro]>P[Pro] Synonymous Variant TLR9 transcript NM_017442.3:c.1635G>A CCG>CCA Coding Sequence Variant toll-like receptor 9 precursor NP_059138.1:p.Pro545= P[Pro]>P[Pro] Synonymous Variant

Kindly guide me on same in details.

https://www.ncbi.nlm.nih.gov/snp/rs352140

Answer 1

[finswimmer]

Hello,

what you are asking for is "How can I describe changes in my sequence compared to a reference sequence?"

So, what you have to answer to yourself:

1. What is my reference sequence? This can be a whole genome (e.g.GRCh37.p13 aka hg19), a chromosome (e.g. NC_000003.11), a gene (e.g. NG_033933.1), a transcript (e.g. NM_017442.3), ...
2. Depending on the reference sequence: At what position is this change? E.g. g.8483 (genomic based), c.1635 (transcript based)
3. How does the change look like? C>A means a C is replace by an A.

So in your example rs352140 there can be two different changes: C>A and C>T.

This change is located at position 52256697 of the chromosome 3 in hg19 (GRCh37) or at position 52222681 in hg38 (GRCh38). Based on the reference sequence of the gene (NG_033933) it's 8483, and on the transcript (NM_017442) it's the 1635 coding base.

As the gene encodes on the reverse strand the base substition given based on gene and transcript is reverse complement.

fin swimmer

Answer 2

[Nawaj Shaikh]

Thanks Fin Swimmer for your valuable comments and guidance, But would you explain why nucleotide is changed when you considered chromosome position 52222681, C to T or C to A (e.g. NC_000003.12:g.52222681 C>T), however in gene it is G to A or G to T (e.g. NG_033933.1:g.8483 G>A) ? Second query is how does g.8483 number comes in gene, as i understand transcript 1635 coding base.

[finswimmer]

Hello,

if you describe the change based on chromosome you always take the positiv strand. If you describe the change based on the gene/transcript you take into account on which strand this gene encodes. So if a gene like TLR9 encodes on the negative strand C becomes G and A becomes T.

To your second question: "g." means you count every base that belongs to your reference (genomic). "c." means you just count every coding base with "A" of the ATG start codon is 1. Every base that belongs to non coding regions like Intron are not counted.

BTW: Have a look at hgvs to read more about the nomenclature.

fin swimmer

[Devon Ryan]

Aren't c. coordinates cDNA? So it's not just coding bases but UTR as well.

Edit: Nevermind, you're correct. I apparently need more coffee today :)

[Nawaj Shaikh]

Thank you very much for your kind guidance.

[Devon Ryan]

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