huCE80FB (23andMe genotype) - GET-Evidence variant report

Variant report for huCE80FB (23andMe genotype)

Log file: 




VariantClinical
Importance
ImpactAllele
freq
Summary
1APOE-C130RHighWell-establishedWell-established pathogenic

Complex/Other, Heterozygous
0.135392This is generally known as the ApoE4 allele of ApoE and is associated with increased risk of Alzheimer's. 20-25% of individuals are heterozygous for this variant, and 1-2% are homozygous. Data from Khachaturian et al. suggests an average 7% of all individuals developed Alzheimer's by the age of 80; when this is split by ApoE4 status: 10% of ApoE4 heterozygotes (3% increased attributable risk), 40% of ApoE4 homozygotes (33% increased attributable risk), and 5% of non-carriers (2% decreased attributable risk). Notably, their model suggests 70-75% of people would eventually develop Alzheimer's by the age of 100 regardless of ApoE4 genotype (and 25-30% are resistant, regardless of genotype), but that ApoE4 variants shift the disease onset to occur significantly earlier (4 years earlier for heterozygous carriers, 13 years for homozygotes).1
2UGT1A1-G71RModerateLikelyLikely pathogenic

Complex/Other, Heterozygous
0.000743632This variant, also known as UGT1A1*6, is associated with Gilbert syndrome (found in ~5% of the population) and transient hyperbilirubinemia in infants in east asian populations. This allele appears to have incomplete penetrance and causes reduced enzyme activity.1
3C3-R102GModerateLikelyLikely pathogenic

Complex/Other, Heterozygous
0.152073This 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%.1
4PPARG-P12AModerateUncertainUncertain not reviewed

Unknown, Heterozygous
0.08867821
5MTRR-I49MLowLikelyLikely pathogenic

Recessive, Carrier (Heterozygous)
0.451199This common variant (HapMap allele frequency of 31.3%) in a protein involved in folate (B9) and cobalamin (B12) metabolism and is often reported as "MTRR I22M" (an alternative transcript position). Mothers homozygous for this variant are associated with having around a increased chance of a child with Down syndrome (risk of 0.4%, average risk in population is 0.25%). Notably, age plays a far larger role in the rate of Down syndrome (risk is 4.5% for a mother 45-years-of-age), and it is unknown how this variant may combine with the effect of age. There are conflicting reports associating this variant with incidence of neural tube defects, possibly when combined with MTHFR A222V.1
6TGFB1-R25PLowUncertainUncertain pathogenic

Complex/Other, Heterozygous
0.0488858This variant in a growth factor gene is associated with variation in TGFB1 levels; this has been associated with various pathogenic and some protective effects, including: more hepatic fibrosis progression in hep C patients, lower risk of cleft palate, anticorrelation with longevity, higher risk of myocardial infarction and lower risk of hypertension.1
7TLR5-R392XLowUncertainUncertain pathogenic

Complex/Other, Heterozygous
0.0439673This variant is believed to impair the ability to generate an immune response to the flagella of the bacteria. It is weakly associated with an increased incidence of Legionnaires' Disease, p = 0.085, increased lifetime risk of disease ~0.88% (about twice average). The variant is also weakly associated with a reduced incidence of systemic lupus erythematosus, p = 0.165.1
8LRP5-A1330VLowUncertainUncertain pathogenic

Complex/Other, Heterozygous
0.110367In a study of a UK population this variant was associated with a small increased risk of osteoporosis and osteoporotic bone fractures, with each copy of the variant presumed to have an additive effect. A study in Chinese young men failed to find an association with peak bone density. 1
9TP53-P72RLowUncertainUncertain pathogenic

Unknown, Heterozygous
0.627743This is a common variant was first reported as a polymorphism. It has since had mixed associations with cancer: Storey et al. conclude a 7x *increased* risk of HPV cancer for homozygotes vs hets, but Jones et al. find a 1.98x *decreased* risk for colorectal cancer. This variant may have significant impact on particular cancers, but it is unclear what effect it has on the overall burden of cancer.1
10SP110-L425SLowUncertainUncertain pathogenic

Unknown, Homozygous
0.863357This variant is associated with a slightly increased risk of tuberculosis. It is unclear whether it is itself causal, or in linkage disequilibrium with some other causal variant that has a stronger effect.1
11WFS1-R611HLowUncertainUncertain not reviewed

Recessive, Carrier (Heterozygous)
0.400446This nonsynonymous SNP is associated with Wolfram Syndrome (known as DIDMOAD), which is characterized by early-onset non-autoimmune diabetes mellitus, diabetes insipidus, optic atrophy, and deafness) and to adult Type Two Diabetes Mellitus. The WFS1 gene maps to chromosome 4p16.3. The variant has been shown to be statistically associated with type II diabetes in six UK studies and one study of Ashkenazi Jews (Sandhu, M., et al., Minton et al.).1
12PRNP-M129VLowWell-establishedWell-established protective

Complex/Other, Homozygous
0.339561This variant is associated with some protective effects for prion disease -- individuals homozygous for this variant are less susceptible to Creutzfeldt-Jakob, and Papua New Guinea individuals heterozygotes at this site are less susceptible to kuru. 1
13CFH-V62ILowLikelyLikely protective

Complex/Other, Homozygous
0.391616Associated with a decreased risk for age related macular degeneration (ARMD). Homozygotes for this have a 4-5% decreased attributable risk (3-4% vs. average 8% risk), heterozygotes have slightly lower than average risk (7%). Non-carriers have an increased risk (12-13%). ARMD impairs sharp vision as age progresses. While there is no cure, treatment can slow progression of the disease and environmental factors (smoking and obesity) contribute to higher risk.1
14ABCG5-R50CLowLikelyLikely protective

Unknown, Heterozygous
0.0684142This variant has a mild protective effect on blood cholesterol. It is associated with slightly lower total and LDL cholesterol levels.1
15KCNJ11-K23ELowLikelyLikely protective

Unknown, Heterozygous
0.738148This variant is associated with decreased risk of type 2 diabetes. It is unclear whether this variant has additive effects, or acts in a dominant or recessive manner. Assuming diabetes has a lifetime risk of 36%, we estimate a decreased risk of around 1-2% per copy of this variant.1
16PMS2-P470SLowLikelyLikely benign

Unknown, Heterozygous
0.374884Benign, common variant.1
17EFHC1-R182HLowLikelyLikely benign

Unknown, Heterozygous
0.0439673Probably benign. OMIM appears to incorrectly interpret literature as linking this variant to juvenile myoclonic epilepsy; the authors report it as a polymorphism.1
18HTRA2-A141SLowLikelyLikely benign

Unknown, Heterozygous
0.016814Probably benign. One report proposed an association with increased risk for Parkinson's disease, but had very weak statistical significance. A later study found an equal incidence of this variant in cases and controls, contradicting any association with the disease.1
19RPGRIP1-A547SLowUncertainUncertain benign

Complex/Other, Heterozygous
0.232202Probably benign. Implicated in causing autosomal recessive cone-rod dystrophy, but a later report found the same incidence in controls and concludes it is not causal.1
20TPCN2-G734ELowUncertainUncertain benign

Unknown, Homozygous
0.286166Pigmentation allele.1
21PTCH1-P1315LLowUncertainUncertain benign

Unknown, Heterozygous
0.29631Common polymorphism, presumed benign.1
22GJB2-V27ILowUncertainUncertain benign

Unknown, Heterozygous
0.00269567Probable non-pathogenic; other variants in gene associated with hearing loss. A few controversial mutations of uncertain or evolving clinical signi´Čücance are included in this prototype. Examples include V27I, M34T, V37I, and E114G in the GJB2 gene and IVS2-2AG in the SLC26A5 gene. This variant is also observed both in Case and Control in the study of hearing loss.1
23EDAR-V370ALowUncertainUncertain benign

Unknown, Heterozygous
0.0105968Associated with thicker hair, common in Chinese and Japanese individuals and thought to be Asian-specific.1
24BRCA1-Q356RLowUncertainUncertain benign

Unknown, Heterozygous
0.0462911One common variant associated this variant with an increased risk of breast cancer, but a more recent, larger study found no association.1
25HR-T1022ALowUncertainUncertain benign

Recessive, Carrier (Heterozygous)
0.0969511Probably benign. One study implicated it in causing alopecia universalis, but a later report noted the variant has an allele frequency inconsistent with the rarity of that disease.1
26PCSK9-G670ELowUncertainUncertain benign

Unknown, Homozygous
0.888269This variant is likely benign. 1
27TAS2R38-I296VLowUncertainUncertain benign

Unknown, Homozygous
0.463376This variant is associated with "taster" status of PTC, along with 49P and 262A. Due to linkage disequilibrium, the independent effects of positions 296 and 262 is unclear. The presence of 49P confers taster status in a dominant fashion, but in the absence of 49P, the presence of 262A/296V is still positively associated with tasting PTC.1
28SLC45A2-L374FLowUncertainUncertain benign

Unknown, Heterozygous
0.691764Pigmentation allele for non-black hair, and consequently, possible increased susceptibility to malignant melanoma.1
29RP1-N985YLowUncertainUncertain benign

Unknown, Heterozygous
0.348671Probably benign. One report linked this variant to high triglycerides, but a later paper found a nearby SNP with similar association and suggests that both findings are caused by linkage to an undiscovered causal variant.1
30TAS2R38-A49PLowUncertainUncertain benign

Unknown, Homozygous
0.431121This variant is strongly associated with causing the "taster" phenotype of phenylthiocarbamine (PTC) in a dominant manner.1
VariantPrioritization scoreAllele
freq
Num of
articles
Zygosity and Prioritization Score Reasons

Gene search

"GENE" or "GENE A123C":

Log in