CETP A390P - GET-Evidence

Curation:
Currentness:

CETP A390P

(CETP Ala390Pro)


Short summary

This variant is associated with slightly lower HDL (good) cholesterol, although it has a negligible effect (around 2 mg/dl).

Variant evidence
Computational 2

Polyphen 2 predicts damaging effect, other variants in this gene associated with similar disease effects

Functional -
Case/Control 4

High significance (p=0.00595

See Spirin V et al. 2007 (17952847).

Familial

No familial data

 
Clinical importance
Severity 3

Heart disease

Treatability 3

Treatable with diet and exercise

Penetrance 1

Very little individual effect on heart disease

See Spirin V et al. 2007 (17952847).

 

Impact

Low clinical importance, Likely pathogenic

(The "low clinical importance, likely" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern

undefined

Summary of published research, and additional commentary

 

Allele frequency

  • C @ chr16:57015091: 3.9% (418/10758) in EVS
  • C @ chr16:55572591: 3.9% (5/128) in GET-Evidence
  • Frequency shown in summary reports: 3.9% (418/10758)

Publications
 

Spirin V, Schmidt S, Pertsemlidis A, Cooper RS, Cohen JC, Sunyaev SR. Common single-nucleotide polymorphisms act in concert to affect plasma levels of high-density lipoprotein cholesterol. Am J Hum Genet. 2007 Dec;81(6):1298-303. PubMed PMID: 17952847; PubMed Central PMCID: PMC2276349.

This variant is reported to have an association with lower HDL cholesterol. The study examined variants in seven genes associated with HDL metabolism. They report p=5.95 * 10^-3 (0.00595) for their validation set with the variant (Table 1).

The authors note “our analysis of all common SNPs in the reverse cholesterol pathway was able to explain only 2.2% of variance of HDL-C level in the DHS population”. Based on figure 1, it looks like each snp allele lowers HDL cholesterol by ~2.5 mg/dl on average. Table 1 lists a regression coefficient of -1.27 — unclear if this in mg/dl units?

Genomes
 

hu241DEA - CGI sample GS01175-DNA_D05 from PGP sample 1205491
het C @ chr16:57015091

 

 

hu4339C0 - CGI sample GS01175-DNA_H01 from PGP sample 94797469
het C @ chr16:57015091

 

hu92C40A - CGI sample GS01175-DNA_G03 from PGP sample 92527586
het C @ chr16:57015091

 

huC30901 - CGI sample GS00253-DNA_B01_200_37
het C @ chr16:57015091

 

GS12004 - var-GS12004-1100-36-ASM
het C @ chr16:55572592

 

GS19735 - var-GS19735-1100-36-ASM
het C @ chr16:55572592

 

Other external references
 

    dbSNP
  • rs5880
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    PolyPhen-2
  • Score: 0.992 (probably damaging)
    Web search results (3 hits -- see all)
  • Common Single-Nucleotide Polymorphisms Act in Concert to ...
    The fourth SNP (CETP A390P [rs5880]) is less common (minor-allele ... However, two SNPs (CETP rs183130 and LPL rs326) had nominally significant interactions ...
    www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2276349
  • Power of deep, all-exon resequencing for discovery of human ...
    Power of deep, all-exon resequencing for discovery of human trait genes ... However, a segregating nonsynonymous SNP A390P in CETP is associated with 0.4σ ...
    www.ncbi.nlm.nih.gov/pmc/articles/PMC2656172/?tool=pubmed
  • Table 3 Text
    ... 152 rs5880 CETP 1071 16 55572592 NM_000078 NP_000069 C/G A390P plus 20419188 1303 SEQUENOM CEPH CEPH ... " 154 rs5881 CETP 1071 16 55569513 NM_000078 NP_000069 A/G G331S ...
    icr.ac.uk/research/research_sections/.../2842.txt

Other in silico analyses
 

  • NBLOSUM100 score = 2
  • GET-Evidence autoscore = 5

Edit history
 

Gene search

"GENE" or "GENE A123C":

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