{"_id":"chr21:g.27264084C>G","_version":1,"cadd":{"_license":"http://bit.ly/2TIuab9","alt":"G","anc":"C","annotype":"CodingTranscript","bstatistic":825,"chmm":{"bivflnk":0.0,"enh":0.008,"enhbiv":0.0,"het":0.0,"quies":0.118,"reprpc":0.0,"reprpcwk":0.008,"tssa":0.0,"tssaflnk":0.0,"tssbiv":0.0,"tx":0.465,"txflnk":0.0,"txwk":0.386,"znfrpts":0.008},"chrom":21,"consdetail":"missense","consequence":"NON_SYNONYMOUS","consscore":7,"cpg":0.04,"dna":{"helt":2.75,"mgw":0.17,"prot":-0.96,"roll":0.44},"encode":{"exp":14405.6,"h3k27ac":3.0,"h3k4me1":4.96,"h3k4me3":2.48,"nucleo":2.3},"exon":"17/18","fitcons":0.701516,"gc":0.46,"gene":{"ccds_id":"CCDS13576.1","cds":{"cdna_pos":2195,"cds_pos":2161,"rel_cdna_pos":0.63,"rel_cds_pos":0.93},"feature_id":"ENST00000346798","gene_id":"ENSG00000142192","genename":"APP","prot":{"domain":"tmhmm","protpos":721,"rel_prot_pos":0.94}},"gerp":{"n":5.65,"rs":659.2,"rs_pval":2.97824e-172,"s":5.65},"grantham":32,"isderived":"TRUE","isknownvariant":"FALSE","istv":"TRUE","length":0,"mapability":{"20bp":1,"35bp":1},"min_dist_tse":27,"min_dist_tss":6212,"mutindex":49,"naa":"L","oaa":"V","phast_cons":{"mammalian":1.0,"primate":0.999,"vertebrate":1.0},"phred":26.1,"phylop":{"mammalian":2.821,"primate":0.651,"vertebrate":5.729},"polyphen":{"cat":"probably_damaging","val":0.999},"pos":27264084,"rawscore":5.425321,"ref":"C","segway":"R1","sift":{"cat":"tolerated","val":0.3},"type":"SNV"},"chrom":"21","dbnsfp":{"_license":"http://bit.ly/2VLnQBz","aa":{"alt":"L","codon_degeneracy":[0,0,0,0,0,0,0,0],"codonpos":[1,1,1,1,1,1,1,1],"pos":[721,590,646,702,611,697,665,703],"ref":"V","refcodon":["GTG","GTG","GTG","GTG","GTG","GTG","GTG","GTG"]},"alphamissense":{"pred":["A","A","A","A","A","B","A","A"],"rankscore":0.65448,"score":[0.3573,0.3762,0.3859,0.5193,0.4558,0.2882,0.4795,0.4843]},"alt":"G","altai_neandertal":["C","C"],"ancestral_allele":"C","appris":["principal4","alternative1","alternative1","alternative1"],"bayesdel":{"add_af":{"pred":"D","rankscore":0.89378,"score":0.390852},"no_af":{"pred":"D","rankscore":0.89243,"score":0.323656}},"bstatistic":{"converted_rankscore":0.013,"score":993.0},"chagyrskaya_neandertal":["C","C"],"chrom":"21","clinpred":{"pred":"D","rankscore":0.45559,"score":0.788010138943999},"dann":{"rankscore":0.84382,"score":0.9975299633958841},"denisova":["C","C"],"deogen2":{"pred":"D","rankscore":0.8876,"score":0.635588},"eigen":{"phred_coding":4.716646,"raw_coding":0.456751466573478,"raw_coding_rankscore":0.64588},"eigen-pc":{"phred_coding":5.738025,"raw_coding":0.558328209651129,"raw_coding_rankscore":0.71981},"ensembl":{"geneid":["ENSG00000142192","ENSG00000142192","ENSG00000142192","ENSG00000142192","ENSG00000142192","ENSG00000142192","ENSG00000142192","ENSG00000142192"],"proteinid":["ENSP00000284981","ENSP00000346129","ENSP00000345463","ENSP00000350578","ENSP00000352760","ENSP00000387483","ENSP00000398879","ENSP00000351796"],"transcriptid":["ENST00000346798","ENST00000354192","ENST00000348990","ENST00000357903","ENST00000359726","ENST00000440126","ENST00000439274","ENST00000358918"]},"esm1b":{"pred":["D","D","D","D","D","D"],"rankscore":0.67329,"score":[-8.849,-7.572,-7.814,-8.52,-8.585,-8.943]},"eve":{"class10_pred":"U","class20_pred":"U","class25_pred":"U","class30_pred":"U","class40_pred":"U","class50_pred":"U","class60_pred":"B","class70_pred":"B","class75_pred":"B","class80_pred":"B","class90_pred":"B","rankscore":0.33111,"score":0.24445110415524},"fathmm":{"converted_rankscore":0.95422,"pred":["D","D","D","D","D","D","D"],"score":[-3.72,-3.72,-3.72,-3.72,-3.72,-3.72,-3.72]},"fathmm-mkl":{"coding_group":"AEFBI","coding_pred":"D","coding_rankscore":0.80611,"coding_score":0.98215},"fathmm-xf":{"coding_pred":"D","coding_rankscore":0.77715,"coding_score":0.859474},"fitcons":{"gm12878":{"confidence_value":2,"rankscore":0.06304,"score":0.389834},"h1-hesc":{"confidence_value":0,"rankscore":0.87919,"score":0.724815},"huvec":{"confidence_value":0,"rankscore":0.83352,"score":0.714379},"integrated":{"confidence_value":0,"rankscore":0.73137,"score":0.706548}},"gencode_basic":["Y","Y","Y","Y","Y","Y","Y","Y"],"genename":["APP","APP","APP","APP","APP","APP","APP","APP"],"genocanyon":{"rankscore":0.74766,"score":0.999999999999962},"gerp":{"91_mammals":{"rankscore":0.77318,"score":4.05}},"gerp++":{"nr":5.65,"rs":5.65,"rs_rankscore":0.86881},"gmvp":{"rankscore":0.87904,"score":0.8793718799827906},"hg18":{"end":26185955,"start":26185955},"hg19":{"end":27264084,"start":27264084},"hg38":{"end":25891772,"start":25891772},"hgvsc":["c.1936G>C","c.2161G>C","c.1768G>C","c.1993G>C","c.2107G>C","c.1831G>C","c.2089G>C","c.2104G>C"],"hgvsp":["p.Val697Leu","p.V665L","p.Val702Leu","p.V697L","p.V590L","p.Val721Leu","p.Val665Leu","p.V721L","p.V611L","p.V702L","p.V703L","p.Val611Leu","p.Val646Leu","p.Val703Leu","p.Val590Leu","p.V646L"],"interpro":{"domain":["Beta-amyloid precursor protein C-terminal","Beta-amyloid precursor protein C-terminal","Beta-amyloid precursor protein C-terminal"]},"list-s2":{"pred":["D","D","D","D","D","D","D","D"],"rankscore":0.81545,"score":[0.950805,0.950805,0.950805,0.950805,0.950805,0.950805,0.950805,0.951905]},"lrt":{"converted_rankscore":0.8433,"omega":0.0,"pred":"D","score":0.0},"m-cap":{"pred":"D","rankscore":0.84804,"score":0.17051},"metalr":{"pred":"D","rankscore":0.93291,"score":0.8017},"metarnn":{"pred":["D","D","D","D","D","D","D","D"],"rankscore":0.75626,"score":[0.7508545,0.7508545,0.7508545,0.7508545,0.7508545,0.7508545,0.7508545,0.7508545]},"metasvm":{"pred":"D","rankscore":0.93213,"score":0.703},"mpc":{"rankscore":0.80838,"score":1.21089657068},"mutationassessor":{"pred":"N","rankscore":0.1252,"score":0.42},"mutationtaster":{"aae":["V721L","V590L","V646L","V702L","V665L","V703L","V665L","V697L","V611L"],"converted_rankscore":0.81001,"model":["simple_aae","simple_aae","simple_aae","simple_aae","simple_aae","simple_aae","simple_aae","simple_aae","simple_aae"],"pred":["D","D","D","D","D","D","D","D","D"],"score":[1.0,1.0,1.0,1.0,1.0,1.0,1.0,1.0,1.0]},"mutformer":{"rankscore":0.96181,"score":0.98586065},"mutpred":{"aa_change":"V721L","accession":"P05067","pred":{"mechanism":"Loss of MoRF binding","p_val":0.1068},"rankscore":0.73706,"score":0.605},"mvp":{"rankscore":0.96529,"score":[0.96566108948,0.96566108948,0.96566108948,0.96566108948,0.96566108948,0.96566108948,0.96566108948,0.96566108948]},"phactboost":{"rankscore":0.84372,"score":0.975892821772941},"phastcons":{"100way_vertebrate":{"rankscore":0.71638,"score":1.0},"17way_primate":{"rankscore":0.97212,"score":1.0},"470way_mammalian":{"rankscore":0.68203,"score":1.0}},"phylop":{"100way_vertebrate":{"rankscore":0.68358,"score":5.751},"17way_primate":{"rankscore":0.4025,"score":0.599},"470way_mammalian":{"rankscore":0.61989,"score":7.613}},"polyphen2":{"hdiv":{"pred":["D","D","P","P","D"],"rankscore":0.7322,"score":[0.996,0.998,0.902,0.902,0.996]},"hvar":{"pred":["D","D","D","D","D"],"rankscore":0.86255,"score":[0.997,0.995,0.927,0.927,0.997]}},"primateai":{"pred":"D","rankscore":0.82672,"score":0.804651379585},"provean":{"converted_rankscore":0.33798,"pred":["N","N","N","N","N","N","N"],"score":[-1.25,-1.31,-1.21,-1.25,-1.25,-1.36,-1.18]},"ref":"C","reliability_index":10,"revel":{"rankscore":0.90982,"score":[0.74,0.74,0.74,0.74,0.74,0.74,0.74,0.74]},"sift":{"converted_rankscore":0.16848,"pred":["T","T","T","T","T","T","T"],"score":[0.268,0.41,0.407,0.292,0.288,0.255,0.269]},"sift4g":{"converted_rankscore":0.1176,"pred":["T","T","T","T","T","T","T","T"],"score":[0.525,0.487,0.525,0.517,0.515,0.507,0.484,0.54]},"siphy_29way":{"logodds_rankscore":0.95998,"logodds_score":19.6915,"pi":{"a":0.0,"c":1.0,"g":0.0,"t":0.0}},"tsl":[1,1,1,1,2,2,1,5],"uniprot":[{"acc":"P05067","entry":"A4_HUMAN"},{"acc":"P05067-10","entry":"A4_HUMAN"},{"acc":"P05067-4","entry":"A4_HUMAN"},{"acc":"P05067-8","entry":"A4_HUMAN"},{"acc":"A0A0A0MRG2","entry":"A0A0A0MRG2_HUMAN"},{"acc":"P05067-11","entry":"A4_HUMAN"},{"acc":"E9PG40","entry":"E9PG40_HUMAN"},{"acc":"P05067-9","entry":"A4_HUMAN"}],"varity":{"er":{"rankscore":0.7096,"score":0.4977722},"er_loo":{"rankscore":0.7096,"score":0.4977722},"r":{"rankscore":0.73677,"score":0.6183929},"r_loo":{"rankscore":0.73678,"score":0.6183929}},"vep_canonical":"YES","vest4":{"rankscore":0.80866,"score":[0.808,0.752,0.75,0.762,0.757,0.797,0.807,0.813]},"vindijia_neandertal":["C","C"]},"hg19":{"end":27264084,"start":27264084},"snpeff":{"_license":"http://bit.ly/2suyRKt","ann":[{"cdna":{"length":"3633","position":"2361"},"cds":{"length":"2313","position":"2161"},"effect":"missense_variant","feature_id":"NM_000484.3","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.2161G>C","hgvs_p":"p.Val721Leu","protein":{"length":"770","position":"721"},"putative_impact":"MODERATE","rank":"17","total":"18","transcript_biotype":"protein_coding"},{"cdna":{"length":"3557","position":"2285"},"cds":{"length":"2241","position":"2089"},"effect":"missense_variant","feature_id":"NM_001136016.3","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.2089G>C","hgvs_p":"p.Val697Leu","protein":{"length":"746","position":"697"},"putative_impact":"MODERATE","rank":"16","total":"17","transcript_biotype":"protein_coding"},{"cdna":{"length":"3240","position":"1968"},"cds":{"length":"1920","position":"1768"},"effect":"missense_variant","feature_id":"NM_001136129.2","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.1768G>C","hgvs_p":"p.Val590Leu","protein":{"length":"639","position":"590"},"putative_impact":"MODERATE","rank":"14","total":"15","transcript_biotype":"protein_coding"},{"cdna":{"length":"3465","position":"2193"},"cds":{"length":"2145","position":"1993"},"effect":"missense_variant","feature_id":"NM_001136130.2","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.1993G>C","hgvs_p":"p.Val665Leu","protein":{"length":"714","position":"665"},"putative_impact":"MODERATE","rank":"16","total":"17","transcript_biotype":"protein_coding"},{"cdna":{"length":"3579","position":"2307"},"cds":{"length":"2259","position":"2107"},"effect":"missense_variant","feature_id":"NM_001204301.1","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.2107G>C","hgvs_p":"p.Val703Leu","protein":{"length":"752","position":"703"},"putative_impact":"MODERATE","rank":"16","total":"17","transcript_biotype":"protein_coding"},{"cdna":{"length":"3522","position":"2250"},"cds":{"length":"2202","position":"2050"},"effect":"missense_variant","feature_id":"NM_001204302.1","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.2050G>C","hgvs_p":"p.Val684Leu","protein":{"length":"733","position":"684"},"putative_impact":"MODERATE","rank":"15","total":"16","transcript_biotype":"protein_coding"},{"cdna":{"length":"3354","position":"2082"},"cds":{"length":"2034","position":"1882"},"effect":"missense_variant","feature_id":"NM_001204303.1","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.1882G>C","hgvs_p":"p.Val628Leu","protein":{"length":"677","position":"628"},"putative_impact":"MODERATE","rank":"14","total":"15","transcript_biotype":"protein_coding"},{"cdna":{"length":"3576","position":"2304"},"cds":{"length":"2256","position":"2104"},"effect":"missense_variant","feature_id":"NM_201413.2","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.2104G>C","hgvs_p":"p.Val702Leu","protein":{"length":"751","position":"702"},"putative_impact":"MODERATE","rank":"16","total":"17","transcript_biotype":"protein_coding"},{"cdna":{"length":"3408","position":"2136"},"cds":{"length":"2088","position":"1936"},"effect":"missense_variant","feature_id":"NM_201414.2","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.1936G>C","hgvs_p":"p.Val646Leu","protein":{"length":"695","position":"646"},"putative_impact":"MODERATE","rank":"15","total":"16","transcript_biotype":"protein_coding"},{"cdna":{"length":"3295","position":"2023"},"cds":{"length":"1983","position":"1831"},"effect":"missense_variant","feature_id":"NM_001136131.2","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.1831G>C","hgvs_p":"p.Val611Leu","protein":{"length":"660","position":"611"},"putative_impact":"MODERATE","rank":"15","total":"16","transcript_biotype":"protein_coding"}]},"vcf":{"alt":"G","position":"27264084","ref":"C"}}