{{Rsnum
|rsid=2230199
|Gene=C3
|Chromosome=19
|position=6718376
|Orientation=minus
|ReferenceAllele=C
|MissenseAllele=G
|GMAF=0.0978
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(C;C)
|geno2=(C;G)
|geno3=(G;G)
|Gene_s=C3
}}{{ population diversity
| geno1=(C;C)
| geno2=(C;G)
| geno3=(G;G)
| CEU | 66.2 | 29.2 | 4.6
| HCB | 100.0 | 0.0 | 0.0
| JPT | 100.0 | 0.0 | 0.0
| YRI | 96.8 | 3.2 | 0.0
| ASW | 0.0 | 0.0 | 0.0
| CHB | 100.0 | 0.0 | 0.0
| CHD | 0.0 | 0.0 | 0.0
| GIH | 0.0 | 0.0 | 0.0
| LWK | 0.0 | 0.0 | 0.0
| MEX | 0.0 | 0.0 | 0.0
| MKK | 0.0 | 0.0 | 0.0
| TSI | 0.0 | 0.0 | 0.0
| HapMapRevision=28
}}[[rs2230199]], a SNP in the complement component [[C3]] gene, has been reported by several investigators to be associated with [[ARMD]]. The common allele at this SNP is known as Arg102; the variant and risk allele is known as Gly102. The risk allele, in orientation to the dbSNP entry for this rs#, is (G).

In one of the largest case-control studies, the odds ratio associated with heterozygotes is 1.61, and for homozygotes, 3.26 (p = 4.5 x 10e-12). {{doi|10.1038/ng2131}}

[http://content.nejm.org/cgi/content/short/357/6/553 NEJM] reports significant associate with [[ARMD]].

[http://thegenesherpa.blogspot.com/2007/08/british-eyes-are-smilingor-degenerating.html blog post]

{{omim
|desc=C3S/C3F POLYMORPHISM
|id=120700
|rsnum=2230199
|variant=0001
}}
{{ neighbor
| rsid = 1047286
| distance = 5125
}}

{{Venter SNP
|rsid=2230199
|allele=C
|frequency=
|uid=1103691081610
|type=heterozygous_SNP
|hugo=C3
|ensembl gene=ENSG00000125730
|ensembl transcript=ENST00000245907
|sift=TOLERATED
|disease=Defects in C3 are the cause of C3 deficiency (MIM:120700). It can result in susceptibility to pyogenic infection.
}}

{{PMID Auto
|PMID=19399715
|Title=Impact of interacting functional variants in COMT on regional gray matter volume in human brain
}}

{{omim
|id=611378
|desc=MACULAR DEGENERATION, AGE-RELATED, 9; ARMD9
|rsnum=2230199
}}
{{PMID Auto
|PMID=19234341
|Title=Complement component 3 (C3) haplotypes and risk of advanced age-related macular degeneration
}}
{{PMID Auto
|PMID=19797206
|Title=Susceptibility genes and progression in age-related maculopathy - a study of single eyes. The prospective Muenster Ageing and Retina Study (MARS)
}}
{{PMID Auto
|PMID=19850835
|Title=The noncoding variant in complement factor H gene increases risk of exudative age-related macular degeneration in a Chinese population
}}

{{PharmGKB
|RSID=rs2230199
|Name_s=C3:Arg80Gly
|Gene_s=C3
|Feature=
|Evidence=PubMed ID:17634448
|Annotation=rs2230199 was found to be associated with risk of age-related macular degeneration in English and Scottish case-control studies.
|Drugs=
|Drug Classes=
|Diseases=Macular Degeneration
|Curation Level=Curated
|PharmGKB Accession ID=PA162356130
}}
{{PMID Auto
|PMID=19899988
|Title=Association of c3 gene polymorphisms with neovascular age-related macular degeneration in a chinese population
}}

{{PMID Auto
|PMID=20157618
|Title=Complement Component 3: an assessment of association with AMD and analysis of gene-gene and gene-environment interactions in a Northern Irish cohort
|OA=1
}}

{{PMID Auto GWAS
|PMID=20385819
|Trait=Age-related macular degeneration
|Title=Genetic variants near TIMP3 and high-density lipoprotein-associated loci influence susceptibility to age-related macular degeneration
|RiskAllele=C
|Pval=1E-10
|OR=1.74
|ORtxt=[1.47-2.06]
|OA=1
}}
{{PMID Auto GWAS
|PMID=20385826
|Trait=Age-related macular degeneration
|Title=Genome-wide association study of advanced age-related macular degeneration identifies a role of the hepatic lipase gene (LIPC)
|RiskAllele=
|Pval=2E-8
|OR=None
|ORtxt=None
|OA=1
}}
{{PMID Auto GWAS
|PMID=20861866
|Trait=None
|Title=Genome-wide association identifies SKIV2L and MYRIP as protective factors for age-related macular degeneration
|RiskAllele=C
|Pval=1E-8
|OR=1.44
|ORtxt=[NR]
|OA=1
}}

{{PMID Auto GWAS
|PMID=21665990
|Trait=None
|Title=Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration.
|RiskAllele=C
|Pval=5E-29
|OR=1.5300
|ORtxt=[NR]
|OA=1
}}

{{PMID Auto
|PMID=21871809
|Title=Complement Factor H Y402H polymorphism is associated with an increased risk of mortality after intracerebral hemorrhage
}}

{{PMID Auto
|PMID=22174912
|Title=A Common Complement C3 Variant Is Associated with Protection against Wet Age-Related Macular Degeneration in a Japanese Population
|OA=1
}}

{{PMID Auto
|PMID=22699975
|Title=Genetic analysis of simultaneous geographic atrophy and choroidal neovascularization
|OA=1
}}

{{PMID Auto
|PMID=22718507
|Title=The investigation of allele and genotype frequencies of human C3 (rs2230199) in south Iranian population
}}

{{ClinVar
|rsid=2230199
|Reversed=1
|FwdREF=C
|FwdALT=G
|REF=G
|ALT=C
|RSPOS=6718387
|CHROM=19
|GMAF=0.0975
|dbSNPBuildID=98
|SSR=0
|SAO=1
|VP=0x05016800000015051f130100
|GENEINFO=C3:718
|GENE_NAME=C3
|GENE_ID=718
|WGT=0
|VC=SNV
|CLNALLE=1
|CLNHGVS=NC_000019.9:g.6718387G>C
|CLNORIGIN=1
|CLNSIG=255
|Tags=RV;PM;PMC;SLO;VLD;G5;HD;GNO;KGPhase1;KGPilot123;KGPROD;OTHERKG;PH3;LSD;MTP;OM
|CAF=0.9022; 0.0978
|CLNACC=RCV000018584.3; RCV000018585.3
|CLNDBN=MACULAR DEGENERATION, AGE-RELATED, 9, SUSCEPTIBILITY TO; C3S/C3F POLYMORPHISM
|CLNSRC=OMIM Allelic Variant
|CLNSRCID=120700.0001
|COMMON=1
|Disease=MACULAR DEGENERATION; C3S/C3F POLYMORPHISM
}}

{{PMID Auto
|PMID=15726497
|Title=Gene-environment interaction effects on the development of immune responses in the 1st year of life.
|OA=1
}}

{{PMID Auto
|PMID=19043567
|Title=Evaluation of clustering and genotype distribution for replication in genome wide association studies: the age-related eye disease study.
|OA=1
}}

{{PMID Auto
|PMID=19048105
|Title=Multifactor effects and evidence of potential interaction between complement factor H Y402H and LOC387715 A69S in age-related macular degeneration.
|OA=1
}}

{{PMID Auto
|PMID=19131662
|Title=A meta-analysis of candidate gene polymorphisms and ischemic stroke in 6 study populations: association of lymphotoxin-alpha in nonhypertensive patients.
|OA=1
}}

{{PMID Auto
|PMID=19169411
|Title=Common variation in the SERPING1 gene is not associated with age-related macular degeneration in two independent groups of subjects.
|OA=1
}}

{{PMID Auto
|PMID=19202148
|Title=Assessing susceptibility to age-related macular degeneration with proteomic and genomic biomarkers.
|OA=1
}}

{{PMID Auto
|PMID=19259132
|Title=Multilocus analysis of age-related macular degeneration.
|OA=1
}}

{{PMID Auto
|PMID=19263529
|Title=Genetic risk factors in recurrent venous thromboembolism: A multilocus, population-based, prospective approach.
|OA=1
}}

{{PMID Auto
|PMID=19330901
|Title=Association of 77 polymorphisms in 52 candidate genes with blood pressure progression and incident hypertension: the Women's Genome Health Study.
|OA=1
}}

{{PMID Auto
|PMID=19381347
|Title=Single nucleotide polymorphisms of the tenomodulin gene (TNMD) in age-related macular degeneration.
|OA=1
}}

{{PMID Auto
|PMID=19559392
|Title=A candidate gene association study of 77 polymorphisms in migraine.
|OA=1
}}

{{PMID Auto
|PMID=19661236
|Title=Plasma complement components and activation fragments: associations with age-related macular degeneration genotypes and phenotypes.
|OA=1
}}

{{PMID Auto
|PMID=19823576
|Title=CFH, C3 and ARMS2 are significant risk loci for susceptibility but not for disease progression of geographic atrophy due to AMD.
|OA=1
}}

{{PMID Auto
|PMID=19828715
|Title=Complement component 3 polymorphisms interact with polyunsaturated fatty acids to modulate risk of metabolic syndrome.
}}

{{PMID Auto
|PMID=20157352
|Title=Genetic analysis of typical wet-type age-related macular degeneration and polypoidal choroidal vasculopathy in Japanese population.
|OA=1
}}

{{PMID Auto
|PMID=20664795
|Title=R102G polymorphism of the C3 gene associated with exudative age-related macular degeneration in a French population.
|OA=1
}}

{{PMID Auto
|PMID=21402993
|Title=Assessing susceptibility to age-related macular degeneration with genetic markers and environmental factors.
}}

{{PMID Auto
|PMID=21455292
|Title=Using genetic variation and environmental risk factor data to identify individuals at high risk for age-related macular degeneration.
|OA=1
}}

{{PMID Auto
|PMID=22273503
|Title=Association of polymorphisms in C2, CFB and C3 with exudative age-related macular degeneration in a Korean population.
}}

{{PMID Auto
|PMID=22361228
|Title=Complement C3 gene polymorphism in renal transplantation (an Iranian experience).
}}

{{PMID Auto GWAS
|PMID=22705344
|Trait=None
|Title=Heritability and Genome-Wide Association Study to Assess Genetic Differences between Advanced Age-Related Macular Degeneration Subtypes.
|RiskAllele=C
|Pval=5E-13
|OR=1.8300
|ORtxt=None
|OA=1
}}

{{GET Evidence
|gene=C3
|aa_change=Arg102Gly
|aa_change_short=R102G
|impact=pathogenic
|qualified_impact=Moderate clinical importance, Likely pathogenic
|inheritance=other
|quality_scores=Array
|dbsnp_id=rs2230199
|overall_frequency_n=1636
|overall_frequency_d=10758
|overall_frequency=0.152073
|n_genomes=10
|n_genomes_annotated=0
|n_haplomes=11
|n_articles=2
|n_articles_annotated=2
|qualityscore_in_silico=1
|qualitycomment_in_silico=Y
|qualityscore_in_vitro=1
|qualitycomment_in_vitro=Y
|qualityscore_case_control=5
|qualitycomment_case_control=Y
|qualityscore_severity=3
|qualitycomment_severity=Y
|qualityscore_treatability=2
|qualitycomment_treatability=Y
|gene_in_genetests=Y
|in_omim=Y
|pph2_score=0.044
|genetests_testable=Y
|nblosum100=6
|autoscore=3
|webscore=N
|n_web_uneval=10
|variant_evidence=1
|clinical_importance=1
|summary_short=This variant (also called C3F) is common in Europeans (10.2% allele frequency), and is associated with age-related macular degeneration. In the US, 1.5% of adults over 40 have the disease, but the incidence increases strongly with age (>15% in women over 80). Assuming an average lifetime risk of ~10%, heterozygous individuals have a ~13% risk and homozygous have ~20%.
}}

{{PMID Auto
|PMID=23337555
|Title=Pharmacogenetics for Genes Associated with Age-Related Macular Degeneration in the Comparison of AMD Treatments Trials (CATT)
|OA=1
}}

{{PMID Auto
|PMID=23582991
|Title=Genetic Influences on the Outcome of Anti-Vascular Endothelial Growth Factor Treatment in Neovascular Age-related Macular Degeneration
}}

{{PMID Auto GWAS
  |PMID=23455636
  |Trait=Age-related macular degeneration
  |Title=Seven new loci associated with age-related macular degeneration.
  |RiskAllele=C
  |Pval=1E-41
  |OR=1.42
  |ORtxt=[1.37-1.47]
  |OA=1
}}

{{PMID Auto
|PMID=23919682
|Title=Complement alternative pathway genetic variation and Dengue infection in the Thai population
|OA=1
}}

{{PMID Auto
|PMID=23068452
|Title=Common polymorphisms in the complement system and susceptiblity to bacterial meningitis.
}}

{{PMID Auto
|PMID=23233260
|Title=Association between polymorphisms of complement pathway genes and age-related macular degeneration in a Chinese population.
|OA=1
}}

{{on chip | 23andMe v2}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}
{{on chip | FTDNA2}}
{{on chip | FTDNA}}
{{on chip | HumanOmni1Quad}}