huB5A0DF (KHull) - GET-Evidence variant report

Variant report for huB5A0DF (KHull)

Log file: 




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

Complex/Other, Homozygous
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
2C3-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
3SLC4A1-E40KModerateUncertainUncertain pathogenic

Recessive, Carrier (Heterozygous)
0.0118052Rare and reported to cause hemolytic anemia in a recessive manner, although insufficient data is published to establish statistical significance. Polyphen 2 predicts a benign effect.1
4COL4A1-Q1334HLowLikelyLikely pathogenic

Dominant, Heterozygous
0.324689This common variant has been associated with arterial stiffness and, in Japanese, a small increased risk of myocardial infarction (MI, a.k.a. heart attack). This last observation supported a dominant effect for this variant and, assuming a lifetime risk of 15% for MI, we estimate carriers have an additional risk of 0.5-3%.1
5MBL2-G54DLowLikelyLikely pathogenic

Recessive, Carrier (Heterozygous)
0.103923This variant is associated with mannose binding protein deficiency which leads to impaired complement system immune response to mannose-rich pathogens. Patients homozygous for this allele or compound heterozygous are likely to have increased susceptibility to infection, but Hellemann et al. report heterosis for intensive care outcomes in heterozygous subjects. The wild-type version of this gene is known as variant allele A, while this is called variant allele B. See R52C (variant D) and G57E (variant C).1
6AMPD1-Q12XLowLikelyLikely pathogenic

Recessive, Carrier (Heterozygous)
0.0930643Causes Adenosine Deaminase Deficiency in a recessive manner. Most of the time individuals do not report symptoms, but when symptoms do exist they to be post-exercise symptoms of muscle weakness, muscle pain, and getting tired more quickly.1
7APOA5-S19WLowLikelyLikely pathogenic

Unknown, Heterozygous
0.0646151This variant, also known as APOA5*3, is associated with higher plasma triglyceride concentrations but no significant correlation with coronary artery disease itself has been found.1
8LRP5-A1330VLowUncertainUncertain pathogenic

Complex/Other, Homozygous
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
9ELAC2-S217LLowUncertainUncertain pathogenic

Complex/Other, Homozygous
0.273471Reported to be associated with increased susceptibility to prostate cancer, but later studies weaken the hypothesis. Xu et al.'s meta-analysis concludes that there is a small but significant increased risk (OR = 1.13). Assuming a lifetime risk of 16% for prostate cancer we calculate this leads to an increased risk of ~1.5% (17.5% total).1
10TP53-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
11SP110-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
12WFS1-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
13H6PD-R453QLowUncertainUncertain pathogenic

Recessive, Carrier (Heterozygous)
0.308886This common variant may have a small pathogenic effect by contributing to cortisone reductase deficiency (a rare abnormality) when homozygous and combined with a serious pathogenic variant. The same authors have tested and ruled out a contribution to polycystic ovary syndrome (similar phenotype, more common disease).1
14ITPA-P32TLowWell-establishedWell-established pharmacogenetic

Recessive, Carrier (Heterozygous)
0.0609779This variant is associated with inosine triphosphate pyrophosphohydrolase deficiency and may be associated with an adverse reaction to thiopurine drugs (which are used as immunosuppressants). Homozygotes have no detectable ITPase activity, individuals compound heterozygous with another less severe mutation also have severely reduced enzyme activity.1
15rs1544410LowUncertainUncertain pharmacogenetic

Unknown, Homozygous
0.351562rs1544410 is a Vitamin D Receptor (VDR) single nucleotide polymorphism. It is unlikely that it has functional significance because it is located in an intron (Liu et. al.), but it is in strong linkage disequilibrium with rs731236 (Dvornyk et al), which is located in an exon. 1
16FUT2-W154XModerateWell-establishedWell-established protective

Recessive, Homozygous
0.490519This recessive protective variant confers resistance to norovirus (which causes stomach flu). 20% of Caucasians and Africans are homozygous for this variant and are "non-secretors": they do not express ABO blood type antigens in their saliva or mucosal surfaces. Most strains of norovirus bind to these antigens in the gut, and so this non-secretor status confers almost total resistantance to most types of norovirus. There are notable exceptions, some strains of norovirus bind a different target and are equally infectious for secretors and non-secretors.1
17NPC1-H215RLowLikelyLikely protective

Complex/Other, Heterozygous
0.295687This variant is associated with a reduced risk of obesity, with an additive effect of -0.084 BMI per allele (an average of 0.54 pounds less, per allele, in a 5'6" individual). 1
18KCNJ11-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
19IL7R-T244ILowLikelyLikely protective

Unknown, Heterozygous
0.210169The reference genome variant for this allele has been associated with a slight increased risk of multiple sclerosis. Thus, this variant can be treated as a "protective" variant -- carriers of this variant are slightly less likely to have MS. Because the disease is rare and the effect of this variant is not very strong, the absolute decreased risk for carriers of this variant is less than .05% (less than 1 in 2000).1
20ARSA-N350SLowWell-establishedWell-established benign

Unknown, Heterozygous
0.183199This common variant (HapMap 24.1% allele frequency) causes a loss of a glycosylation site (affecting the size of the protein when studied with gel electrophoresis) but does not affect enzyme activity or stability.1
21PMS2-P470SLowLikelyLikely benign

Unknown, Homozygous
0.374884Benign, common variant.1
22LOXL1-R141LLowUncertainUncertain benign

Complex/Other, Homozygous
0.255899Associated with exfoliative glaucoma & syndrome (XFG & XFS) in various populations, but with contradicting results (protective in Caucasians, pathogenic in Japanese). Based on this it seems the variation itself -- although it affects protein structure -- is not itself causing disease. Instead it is likely associated with other nearby causal variants. As such, it is evaluated as benign by GET-Evidence (which focuses on reporting causal variants). See detailed variant report for disease risk associations.1
23RPGRIP1-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
24CD19-R514HLowUncertainUncertain benign

Unknown, Heterozygous
0.0482432Presumed benign.1
25NTRK1-G613VLowUncertainUncertain benign

Unknown, Heterozygous
0.0429448Also called G607V, this variant has been reported as a nonpathogenic polymorphism.1
26NTRK1-H604YLowUncertainUncertain benign

Unknown, Heterozygous
0.0431307Various databases and papers treat this variant as a non-pathogenic polymorphism, although it is fairly uncommon and is computational methods predict it to be damaging.1
27ATM-S707PLowUncertainUncertain benign

Unknown, Heterozygous
0.00818148Probably not pathogenic, several papers conclude it is not associated with breast cancer.1
28PCCA-I475VLowUncertainUncertain benign

Unknown, Heterozygous
0.0377394Reported as a polymorphism, tentatively presumed benign.1
29TPCN2-G734ELowUncertainUncertain benign

Unknown, Heterozygous
0.286166Pigmentation allele.1
30PCSK9-G670ELowUncertainUncertain benign

Unknown, Homozygous
0.888269This variant is likely benign. 1
31RP1-N985YLowUncertainUncertain benign

Unknown, Homozygous
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
32AMPD1-P48LLowUncertainUncertain benign

Unknown, Heterozygous
0.0940695Probably benign, ancestral to15173240 pathogenic Q12X mutation.1
33SLC45A2-L374FLowUncertainUncertain benign

Unknown, Homozygous
0.691764Pigmentation allele for non-black hair, and consequently, possible increased susceptibility to malignant melanoma.1
34PHYH-P29SLowUncertainUncertain benign

Unknown, Homozygous
0.155326Probably benign. This variant was implicated as causing Refsum Disease in a recessive manner, but a subsequent publication noted that all instances were linked with other explanatory mutations. The high allele frequency of this variant in the population (7-13%) contradicts a pathogenic hypothesis.1
35PTCH1-P1315LLowUncertainUncertain benign

Unknown, Heterozygous
0.29631Common polymorphism, presumed benign.1
VariantPrioritization scoreAllele
freq
Num of
articles
Zygosity and Prioritization Score Reasons

Gene search

"GENE" or "GENE A123C":

Log in