<p><strong>Background</strong>: I have been working on a human variant calling pipeline, from whole exome reads to variant annotation.
For variant annotation I used the <a href="https://www.ensembl.org/info/docs/tools/vep/script/vep_cache.html#:%7E:text=For%20most%20of%20the%20functionality,database%20(e.g.%20homo_sapiens_core_109_38)%20installed." rel="nofollow noreferrer">Variant Effect predictor (VEP)</a>, which is <a href="https://www.ensembl.org/index.html" rel="nofollow noreferrer">Ensembl</a> based.</p>
<p>I have used the <a href="https://www.ncbi.nlm.nih.gov/" rel="nofollow noreferrer">NCBI</a> reference genome GRCh38.p14 and the older version GRCh37.p13. The latter version was for comparison with older variant calling pipelines. It is about the latter geneome version I want to continue the discussion.</p>
<p><strong>Problem</strong>: I sparked a little discussion due to the use of different versions of &quot;hg19&quot; genome (GRCH19, B37, NCBI, Ensembl) in a research project. This is related to <a href="https://gatk.broadinstitute.org/hc/en-us/articles/360035890711-GRCh37-hg19-b37-humanG1Kv37-Human-Reference-Discrepancies" rel="nofollow noreferrer">this article</a>. Due to discrepancies in these versions, I also wholeheartedly believe these cannot be used interchangeably. But this also got me thinking about using VEP, based on Ensembl and likely their reference genome, while I also used in my pipeline the reference genome of NCBI. When I look at just two example genes, you can already notice the difference:</p>
<p><a href="https://i.sstatic.net/UCUcq.png" rel="nofollow noreferrer"><img src="https://i.sstatic.net/UCUcq.png" alt="enter image description here" /></a></p>
<p><strong>Question 1</strong>: is VEP able to correctly annotate variants likely based on the Ensembl reference genome, while I am using the NCBI reference genome?</p>
<p><strong>Question 2</strong>: any thought/knowledge on using the one or the other reference genome, Ensembl or NCBI?</p>
<p><strong>Question 3</strong>: Follow-up on Question 2, how do these versions relate to the UCSC version? There does not seem to be a cache for this version?</p>

CC BY-SA 4.0
2023-06-26T18:53:55.160Z
VEP asks you to pick a specific cache when you annotate, so you choose if you want NCBI or EnsEMBL. I prefer the latter because it is comprehensive
Ram RS
CC BY-SA 4.0
2023-06-27T14:28:30.487Z
Hi, please don't answer the question in the question body, write it as a seperate answer to the question.
user438383
<variant-calling><reference-genome><ensembl><ncbi><vep>
Different human reference genomes from NCBI and ENSEMBL, and variant annotation with Variant Effect Predictor (VEP)
# Different human reference genomes from NCBI and ENSEMBL, and variant annotation with Variant Effect Predictor (VEP)

(Asked by: username_0 on 2023-06-26)

**Background**: I have been working on a human variant calling pipeline, from whole exome reads to variant annotation.
For variant annotation I used the [Variant Effect predictor (VEP)](https://www.ensembl.org/info/docs/tools/vep/script/vep_cache.html#:%7E:text=For%20most%20of%20the%20functionality,database%20(e.g.%20homo_sapiens_core_109_38)%20installed.), which is [Ensembl](https://www.ensembl.org/index.html) based.

I have used the [NCBI](https://www.ncbi.nlm.nih.gov/) reference genome GRCh38.p14 and the older version GRCh37.p13. The latter version was for comparison with older variant calling pipelines. It is about the latter geneome version I want to continue the discussion.

**Problem**: I sparked a little discussion due to the use of different versions of "hg19" genome (GRCH19, B37, NCBI, Ensembl) in a research project. This is related to [this article](https://gatk.broadinstitute.org/hc/en-us/articles/360035890711-GRCh37-hg19-b37-humanG1Kv37-Human-Reference-Discrepancies). Due to discrepancies in these versions, I also wholeheartedly believe these cannot be used interchangeably. But this also got me thinking about using VEP, based on Ensembl and likely their reference genome, while I also used in my pipeline the reference genome of NCBI. When I look at just two example genes, you can already notice the difference:

[![enter image description here](https://i.sstatic.net/UCUcq.png)](https://i.sstatic.net/UCUcq.png)

**Question 1**: is VEP able to correctly annotate variants likely based on the Ensembl reference genome, while I am using the NCBI reference genome?

**Question 2**: any thought/knowledge on using the one or the other reference genome, Ensembl or NCBI?

**Question 3**: Follow-up on Question 2, how do these versions relate to the UCSC version? There does not seem to be a cache for this version?

**Tags:** variant-calling, reference-genome, ensembl, ncbi, vep
> **Comments:**
> **username_1**: VEP asks you to pick a specific cache when you annotate, so you choose if you want NCBI or EnsEMBL. I prefer the latter because it is comprehensive  
> **username_2**: Hi, please don't answer the question in the question body, write it as a seperate answer to the question.  

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## 0 answers

