Variant "MC1R:c.478C>T(p.Arg160Trp)"
Search results: 2 records
Variant information
Gene:
MC1R 
Variant:
MC1R:c.478C>T(p.Arg160Trp) 
Genomic location:
chr16:89986144(hg19) 
HGVS:
SO Term RefSeq
protein_coding NM_002386.3:c.478C>T(p.Arg160Trp)
protein_coding NM_006086.3:c.-3666C>T
protein_coding NM_001197181.1:c.-13782C>T
dbSNP ID:
rs1805008  
GWAS trait:
self reported educational attainment,hair color,sunburn 
Modifier statisitcs
Record:
2 
Disorder:
2 
Reference:
2 
Effect type:
Expressivity(1) ,Penetrance(1)  
Modifier effect:
Altered incidence(1) ,Altered onset time(1)  
Details：
  • Target disease:
    Melanoma (DOID_1909)
    Effect type:
    Penetrance 
    Modifier effect:
    Altered incidence 
    Evidence:
    Pooled RHC variants increased also significantly CDKN2A penetrance (OR=2.30; 95% CI 1.15-4.59; P=0.02). 
    Effect:
    Melanocortin-1 receptor (MC1R) gene variants and dysplastic nevi modify penetrance of CDKN2A mutations in French melanoma-prone pedigrees
    Reference:
    PMID16214921
    Title:
    Melanocortin-1 receptor (MC1R) gene variants and dysplastic nevi modify penetrance of CDKN2A mutations in French melanoma-prone pedigrees.
    Species studied:
    Human
    Abstract:
    Germline mutations in CDKN2A gene predispose to melanoma with high but incomplete penetrance. Penetrance of CDKN2A gene was found to be significantly influenced by host factors (nevus phenotypes and sunburn) on one hand and by variants of MC1R gene (RHC variants consistently associated with red hair and fair skin) on the other hand. Our goal was to examine the joint effects of MC1R variants and other potential risk factors [total nevi, dysplastic nevi, pigmentary traits (skin, hair and eye color), skin reactions to sunlight, and degree of sun exposure] on CDKN2A penetrance. Clinical, genetic, and covariate data were recorded in 20 French melanoma-prone families with cosegregating CDKN2A mutations. Analysis of the cotransmission of melanoma and CDKN2A mutations was conducted by likelihood-based methods using the regressive logistic models, which can account for a variation of disease risk with age and can include the aforementioned risk factors as covariates. RHC variants, considered either alone or in the presence of pigmentation and nevus phenotypes, were found to increase significantly CDKN2A penetrance. Multivariate analysis, using a stepwise selection procedure, showed significant effects of two factors on melanoma risk in CDKN2A mutations carriers: RHC variants [odds ratio of hazard function (OR), 2.21; P = 0.03] and dysplastic nevi (OR, 2.93; P < 0.01). Such results may have important consequences to improve the prediction of melanoma risk in families.
  • Target disease:
    Multiple Sclerosis (DOID_2377)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered onset time 
    Evidence:
    P=0.010-0.041 
    Effect:
    PSMG4 p.W99R and NLRP5 p.R761L were found to correlate with an earlier age at MS clinical onset, and MC1R p.R160W with delayed onset of clinical symptoms (p=0.010-0.041).
    Reference:
    PMID28501589
    Title:
    Genetic modifiers of multiple sclerosis progression, severity and onset.
    Species studied:
    Human
    Abstract:
    The genetic contribution to clinical outcomes for multiple sclerosis (MS) has yet to be defined. We performed exome sequencing analysis in 100 MS patients presenting opposite extremes of clinical phenotype (discovery cohort), and genotyped variants of interest in 2016 MS patients (replication cohort). Linear and logistic regression analyses were used to identify significant associations with disease course, severity and onset. Our analysis of the discovery cohort nominated 38 variants in 21 genes. Replication analysis identified PSMG4 p.W99R and NLRP5 p.M459I to be associated with disease severity (p=0.002 and 0.008). CACNA1H p.R1871Q was found associated with patients presenting relapsing remitting MS at clinical onset (p=0.028) whereas NLRP5 p.M459I and EIF2AK1 p.K558R were associated with primary progressive disease (p=0.031 and 0.023). In addition, PSMG4 p.W99R and NLRP5 p.R761L were found to correlate with an earlier age at MS clinical onset, and MC1R p.R160W with delayed onset of clinical symptoms (p=0.010-0.041).