GCKR L446P - GET-Evidence

Note: This variant has not been sufficiently evaluated by a GET-Evidence editor.

To be considered sufficiently evaluated a variant must have both "variant evidence" and "clinical importance" scores filled in.

Please help improve GET-Evidence by evaluating evidence for this variant!

Curation:
Currentness:

GCKR L446P

(GCKR Leu446Pro)


Short summary

 

Variant evidence
Computational 3

PolyPhen: Benign, score 0.000
SIFT: Tolerated 1.00
GVGD: GV 97.78; GD 0.00; Class C0
Variant Effect Predictor (Ensembl ):
SIFT=tolerated(0.78);
PolyPhen=benign(0);
Condel=neutral(0.250)
Mutation Tasting Prediction: Polymorphism, P value: 0.999769; protein features (might be) affected (aa 320-499 DOMAIN SIS 2 gets lost)

Functional -
Case/Control -
Familial -
 
Clinical importance
Severity -
Treatability -
Penetrance -
 

Impact

Insufficiently evaluated pharmacogenetic

(The "insufficiently evaluated" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern

unknown

Summary of published research, and additional commentary

 

Allele frequency

  • C @ chr2:27730940: 67.9% (7302/10758) in EVS
  • C @ chr2:27584443: 69.5% (89/128) in GET-Evidence
  • Frequency shown in summary reports: 67.9% (7302/10758)

Publications
 

Chasman DI, Paré G, Zee RY, Parker AN, Cook NR, Buring JE, Kwiatkowski DJ, Rose LM, Smith JD, Williams PT, Rieder MJ, Rotter JI, Nickerson DA, Krauss RM, Miletich JP, Ridker PM. Genetic loci associated with plasma concentration of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein A1, and Apolipoprotein B among 6382 white women in genome-wide analysis with replication. Circ Cardiovasc Genet. 2008 Oct;1(1):21-30. PubMed PMID: 19802338; PubMed Central PMCID: PMC2630707.

 

Saxena R, Hivert MF, Langenberg C, Tanaka T, Pankow JS, Vollenweider P, Lyssenko V, Bouatia-Naji N, Dupuis J, Jackson AU, Kao WH, Li M, Glazer NL, Manning AK, Luan J, Stringham HM, Prokopenko I, Johnson T, Grarup N, Boesgaard TW, Lecoeur C, Shrader P, O'Connell J, Ingelsson E, Couper DJ, Rice K, Song K, Andreasen CH, Dina C, Köttgen A, Le Bacquer O, Pattou F, Taneera J, Steinthorsdottir V, Rybin D, Ardlie K, Sampson M, Qi L, van Hoek M, Weedon MN, Aulchenko YS, Voight BF, Grallert H, Balkau B, Bergman RN, Bielinski SJ, Bonnefond A, Bonnycastle LL, Borch-Johnsen K, Böttcher Y, Brunner E, Buchanan TA, Bumpstead SJ, Cavalcanti-Proença C, Charpentier G, Chen YD, Chines PS, Collins FS, Cornelis M, J Crawford G, Delplanque J, Doney A, Egan JM, Erdos MR, Firmann M, Forouhi NG, Fox CS, Goodarzi MO, Graessler J, Hingorani A, Isomaa B, Jørgensen T, Kivimaki M, Kovacs P, Krohn K, Kumari M, Lauritzen T, Lévy-Marchal C, Mayor V, McAteer JB, Meyre D, Mitchell BD, Mohlke KL, Morken MA, Narisu N, Palmer CN, Pakyz R, Pascoe L, Payne F, Pearson D, Rathmann W, Sandbaek A, Sayer AA, Scott LJ, Sharp SJ, Sijbrands E, Singleton A, Siscovick DS, Smith NL, Sparsø T, Swift AJ, Syddall H, Thorleifsson G, Tönjes A, Tuomi T, Tuomilehto J, Valle TT, Waeber G, Walley A, Waterworth DM, Zeggini E, Zhao JH; GIANT consortium; MAGIC investigators, Illig T, Wichmann HE, Wilson JF, van Duijn C, Hu FB, Morris AD, Frayling TM, Hattersley AT, Thorsteinsdottir U, Stefansson K, Nilsson P, Syvänen AC, Shuldiner AR, Walker M, Bornstein SR, Schwarz P, Williams GH, Nathan DM, Kuusisto J, Laakso M, Cooper C, Marmot M, Ferrucci L, Mooser V, Stumvoll M, Loos RJ, Altshuler D, Psaty BM, Rotter JI, Boerwinkle E, Hansen T, Pedersen O, Florez JC, McCarthy MI, Boehnke M, Barroso I, Sladek R, Froguel P, Meigs JB, Groop L, Wareham NJ, Watanabe RM. Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge. Nat Genet. 2010 Feb;42(2):142-8. Epub 2010 Jan 17. PubMed PMID: 20081857; PubMed Central PMCID: PMC2922003.

 

Genomes
 

 

hu034DB1 - CGI sample GS00253-DNA_A02_200_37
hom C @ chr2:27730940

 

hu04FD18 - CGI sample GS00253-DNA_F01_200_37
het C @ chr2:27730940

 

hu0D879F - CGI sample GS00253-DNA_G01_200_37
het C @ chr2:27730940

 

 

 

 

 

 

 

 

 

 

 

hu43860C - CGI sample GS00253-DNA_A01_200_37
het C @ chr2:27730940

 

 

 

hu604D39 - CGI sample GS00253-DNA_B02_200_37
hom C @ chr2:27730940

 

 

 

 

 

 

hu9385BA - CGI sample GS00253-DNA_E01_200_37
hom C @ chr2:27730940

 

 

 

huAE6220 - CGI sample GS00253-DNA_H01_200_37
het C @ chr2:27730940

 

huBEDA0B - CGI sample GS00253-DNA_C01_200_37
het C @ chr2:27730940

 

huC30901 - CGI sample GS00253-DNA_B01_200_37
hom C @ chr2:27730940

 

 

 

GS06985 - var-GS06985-1100-36-ASM
het C @ chr2:27584444

 

GS06994 - var-GS06994-1100-36-ASM
het C @ chr2:27584444

 

GS07357 - var-GS07357-1100-36-ASM
het C @ chr2:27584444

 

GS10851 - var-GS10851-1100-36-ASM
het C @ chr2:27584444

 

GS12004 - var-GS12004-1100-36-ASM
het C @ chr2:27584444

 

GS18501 - var-GS18501-1100-36-ASM
het C @ chr2:27584444

 

GS18502 - var-GS18502-1100-36-ASM
hom C @ chr2:27584444

 

GS18504 - var-GS18504-1100-36-ASM
hom C @ chr2:27584444

 

GS18505 - var-GS18505-1100-36-ASM
het C @ chr2:27584444

 

GS18508 - var-GS18508-1100-36-ASM
hom C @ chr2:27584444

 

GS18517 - var-GS18517-1100-36-ASM
hom C @ chr2:27584444

 

GS18526 - var-GS18526-1100-36-ASM
het C @ chr2:27584444

 

GS18555 - var-GS18555-1100-36-ASM
het C @ chr2:27584444

 

GS18558 - var-GS18558-1100-36-ASM
het C @ chr2:27584444

 

GS18940 - var-GS18940-1100-36-ASM
hom C @ chr2:27584444

 

GS18942 - var-GS18942-1100-36-ASM
het C @ chr2:27584444

 

GS18947 - var-GS18947-1100-36-ASM
hom C @ chr2:27584444

 

GS19017 - var-GS19017-1100-36-ASM
het C @ chr2:27584444

 

GS19020 - var-GS19020-1100-36-ASM
hom C @ chr2:27584444

 

GS19025 - var-GS19025-1100-36-ASM
hom C @ chr2:27584444

 

GS19026 - var-GS19026-1100-36-ASM
het C @ chr2:27584444

 

GS19129 - var-GS19129-1100-36-ASM
hom C @ chr2:27584444

 

GS19238 - var-GS19238-1100-36-ASM
het C @ chr2:27584444

 

GS19239 - var-GS19239-1100-36-ASM
hom C @ chr2:27584444

 

GS19240 - var-GS19240-1100-36-ASM
het C @ chr2:27584444

 

GS19648 - var-GS19648-1100-36-ASM
hom C @ chr2:27584444

 

GS19649 - var-GS19649-1100-36-ASM
het C @ chr2:27584444

 

GS19669 - var-GS19669-1100-36-ASM
hom C @ chr2:27584444

 

GS19670 - var-GS19670-1100-36-ASM
hom C @ chr2:27584444

 

GS19700 - var-GS19700-1100-36-ASM
het C @ chr2:27584444

 

GS19701 - var-GS19701-1100-36-ASM
hom C @ chr2:27584444

 

GS19703 - var-GS19703-1100-36-ASM
hom C @ chr2:27584444

 

GS19704 - var-GS19704-1100-36-ASM
hom C @ chr2:27584444

 

GS19735 - var-GS19735-1100-36-ASM
het C @ chr2:27584444

 

GS19834 - var-GS19834-1100-36-ASM
hom C @ chr2:27584444

 

GS20502 - var-GS20502-1100-36-ASM
het C @ chr2:27584444

 

GS20509 - var-GS20509-1100-36-ASM
het C @ chr2:27584444

 

GS21767 - var-GS21767-1100-36-ASM
hom C @ chr2:27584444

 

Other external references
 

    dbSNP
  • rs1260326
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    GWAS
  • Triglycerides (rs1260326-T)
    Kathiresan 7-Dec-08 in Nat Genet
    OR or beta: 0.12 [0.08-0.16] SD increase
    Risk allele frequency: 0.45
    p-value: 2.00E-31
    Initial sample: 19,840 individuals
    Replication sample: Up to 20,623 individuals
    www.ncbi.nlm.nih.gov/pubmed/19060906
  • Other metabolic traits (rs1260326-A)
    Sabatti 7-Dec-08 in Nat Genet
    OR or beta: 0.09 [0.06-0.12] mmol/l increase
    Risk allele frequency: 0.35
    p-value: 4.00E-10 (TG)
    Initial sample: 4,763 individuals
    Replication sample: NR
    www.ncbi.nlm.nih.gov/pubmed/19060910
  • Waist circumference and related phenotypes (rs1260326-?)
    Chambers 4-May-08 in Nat Genet
    OR or beta: NR NR
    p-value: 4.00E-08 (triglycerides)
    Initial sample: 2,684 Asian Indian men
    Replication sample: 11,955 Asian Indian and European individuals
    www.ncbi.nlm.nih.gov/pubmed/18454146
    PolyPhen-2
  • Score: 0 (benign)

Other in silico analyses
 

  • NBLOSUM100 score = 7
  • GET-Evidence autoscore = 2

Edit history
 

Gene search

"GENE" or "GENE A123C":

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