Table 3.
Frequency and bioinformatics analysis of identified variants in ANGPTL3 in FCHL cases and controls.
| Variant | Location | Nucleotide change | Protein change | Bioinformatics analysis | Allele frequency in the general population | Allele frequency in our study | ACMG classificatione | MicroRNAsf | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PredictSNP2a (probability) | FruitFlyb | GnomADc | 1000 Genomes Projectd | Normolipemic subjects | FCHL subjects | p | ||||||
| rs72649573 | Exon 1 | c.379C>T | p.(Leu127Phe) | Deleterious (82%) | NA | 0.00711 | 0.0020 | 0.000 | 0.003 | 0.313 | Benigng | NR |
| – | Intron 1 | c.496-88T>G | NA | Neutral (88%) | Not splicing change | – | – | 0.000 | 0.003 | 0.313 | – | – |
| rs111414963 | Exon 2 | c.565T>C | p.(Leu189Leu) | Neutral (88%) | Not splicing change | 0.00025 | 0.0008 | 0.003 | 0.000 | 0.313 | Likely benign | NR |
| rs531071581 | Intron 2 | c.607-120A>G | NA | Neutral (88%) | Not splicing change | 0.00013 | 0.0006 | 0.000 | 0.003 | 0.313 | – | NR |
| rs72649576 | Intron 2 | c.607-109T>C | NA | Neutral (88%) | Not splicing change | 0.01079 | 0.0042 | 0.024 | 0.003 | 0.020 | – | NR |
| rs72649577 | Intron 2 | c.607-47_607-46delGT | NA | Neutral (88%) | NA | 0.02222 | 0.0136 | 0.022 | 0.003 | 0.031 | – | NR |
| rs185472483 | Intron 3 | c.835+41C>A | NA | – | Not splicing change | 0.00032 | 0.0006 | 0.000 | 0.012 | 0.043 | – | NR |
| rs747725081 | Exon 6 | c.961T>A | p.(Tyr321Asn) | Neutral (88%) | NA | NR | NR | 0.000 | 0.003 | 0.313 | – | NR |
| rs12563308 | Exon 6 | c.1003T>C | p.(Leu335Leu) | Neutral (88%) | NA | 0.03550 | 0.0559 | 0.003 | 0.003 | 0.989 | VUSg | NR |
| rs199555921 | Exon 6 | c.1028A>G | p.(His343Arg) | Neutral (89%) | NA | 0.00016 | NR | 0.003 | 0.000 | 0.321 | – | NR |
| rs763259225 | Exon 6 | c.1089T>G | p.(Val363Val) | Neutral (96%) | NA | NR | NR | 0.003 | 0.000 | 0.321 | – | NR |
| rs145086916 | Exon 6 | c.1122G>A | p.(Pro374Pro) | Neutral (96%) | NA | 0.00077 | 0.0006 | 0.003 | 0.000 | 0.321 | – | NR |
| rs72651034 | Intron 6 | c.1198+111G>A | NA | – | Not splicing change | NR | NR | 0.003 | 0.003 | 0.989 | – | NR |
| rs908541128 | Intron 6 | c.1198+140T>C | NA | – | Not splicing change | 0.000 | 0.000 | 0.003 | 0.000 | 0.321 | – | NR |
| rs34483103 | 3′UTR | c.*52_*60del | NA | – | NA | 0.33531 | 0.3484 | 0.276 | 0.102 | < 0.001 | – |
hsa-miR-151a-3p hsa-miR-7702 |
| – | 3′UTR | c.*76T>G | NA | – | NA | – | – | 0.000 | 0.003 | 0.313 | – | – |
NR not reported, NA not applicable, VUS variant of uncertain significance.
aPredictSNP2 uses CADD, DANN, FATHMM and Funseq2 as predictors.
bFruitFly. New prediction score 0.87 (wild type score 0.89).
cGnomAD. https://gnomad.broadinstitute.org/
d1000 Genomes Project Consortium, Abecasis GR, Auton A, Books LD et al. An integrated map of genetic variation from 1092 human genomes. Nature 2012;491:56–65.
eRichards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015 May;17(5):405–24. https://doi.org/10.1038/gim.2015.30. Epub 2015 Mar 5. PMID: 25741868; PMCID: PMC4544753.
fPolymiRTS Database 3.0: http://compbio.uthsc.edu/miRSNP/
gTikka A, Metso J, Jauhiainen M. ANGPTL3 serum concentration and rare genetic variants in Finnish population. Scand J Clin Lab Invest. 2017;77:601–609.