{"_id":"chr21:g.25891733C>G","_version":1,"chrom":"21","clingen":{"caid":"CA409805435"},"dbnsfp":{"_license":"http://bit.ly/2VLnQBz","aa":{"alt":"R","codon_degeneracy":[0,0,0,0,0,0,0,0],"codonpos":[1,1,1,1,1,1,1,1],"pos":[734,603,659,715,624,710,678,716],"ref":"G","refcodon":["GGT","GGT","GGT","GGT","GGT","GGT","GGT","GGT"]},"alphamissense":{"pred":["P","P","P","P","P","P","P","P"],"rankscore":0.94731,"score":[0.9678,0.9888,0.9841,0.9932,0.9904,0.9743,0.9889,0.9819]},"alt":"G","altai_neandertal":["C","C"],"ancestral_allele":"C","appris":["principal4","alternative1","alternative1","alternative1"],"bayesdel":{"add_af":{"pred":"D","rankscore":0.95358,"score":0.537849},"no_af":{"pred":"D","rankscore":0.95289,"score":0.534807}},"bstatistic":{"converted_rankscore":0.013,"score":993.0},"cadd":{"phred":27.4,"raw_rankscore":0.8067,"raw_score":4.905687},"chagyrskaya_neandertal":["C","C"],"chrom":"21","clinpred":{"pred":"D","rankscore":0.89441,"score":0.996485590934753},"dann":{"rankscore":0.98917,"score":0.999236898252384},"denisova":["C","C"],"deogen2":{"pred":"D","rankscore":0.95206,"score":0.808994},"eigen":{"phred_coding":11.11222,"raw_coding":0.902410103359702,"raw_coding_rankscore":0.91877},"eigen-pc":{"phred_coding":12.52081,"raw_coding":0.869883801015854,"raw_coding_rankscore":0.94121},"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":0.90256,"score":[-11.958,-13.222,-13.11,-12.145,-12.129,-11.874]},"eve":{"class10_pred":"U","class20_pred":"U","class25_pred":"U","class30_pred":"U","class40_pred":"U","class50_pred":"U","class60_pred":"P","class70_pred":"P","class75_pred":"P","class80_pred":"P","class90_pred":"P","rankscore":0.83559,"score":0.7535429277219179},"fathmm":{"converted_rankscore":0.97606,"pred":["D","D","D","D","D","D","D","D"],"score":[-4.48,-4.48,-4.48,-4.48,-4.02,-4.48,-4.48,-4.48]},"fathmm-mkl":{"coding_group":"AEFBI","coding_pred":"D","coding_rankscore":0.93605,"coding_score":0.99261},"fathmm-xf":{"coding_pred":"D","coding_rankscore":0.96084,"coding_score":0.948821},"fitcons":{"gm12878":{"confidence_value":0,"rankscore":0.6231,"score":0.659464},"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":0.98855,"score":0.9886158576271136},"hg18":{"end":26185916,"start":26185916},"hg19":{"end":27264045,"start":27264045},"hg38":{"end":25891733,"start":25891733},"hgvsc":["c.1870G>C","c.1975G>C","c.2032G>C","c.2128G>C","c.2146G>C","c.2200G>C","c.2143G>C","c.1807G>C"],"hgvsp":["p.G715R","p.G716R","p.Gly715Arg","p.G710R","p.Gly624Arg","p.Gly710Arg","p.Gly716Arg","p.Gly603Arg","p.Gly678Arg","p.Gly734Arg","p.G624R","p.G659R","p.Gly659Arg","p.G603R","p.G678R","p.G734R"],"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":0.98527,"score":[0.9958,0.994547,0.994547,0.9958,0.994547,0.9958,0.9958,0.994547]},"lrt":{"converted_rankscore":0.8433,"omega":0.0,"pred":"D","score":0.0},"m-cap":{"pred":"D","rankscore":0.95825,"score":0.548316},"metalr":{"pred":"D","rankscore":0.98379,"score":0.9502},"metarnn":{"pred":["D","D","D","D","D","D","D","D"],"rankscore":0.95175,"score":[0.95796967,0.95796967,0.95796967,0.95796967,0.95796967,0.95796967,0.95796967,0.95796967]},"metasvm":{"pred":"D","rankscore":0.99172,"score":1.0883},"mpc":{"rankscore":0.83916,"score":1.34376536325},"mutationassessor":{"pred":"M","rankscore":0.53209,"score":1.965},"mutationtaster":{"aae":["G734R","G603R","G659R","G715R","G678R","G716R","G678R","G710R","G624R"],"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":0.97406,"score":0.9937425},"mutpred":{"aa_change":"G734R","accession":"P05067","pred":{"mechanism":"Gain of MoRF binding","p_val":0.0215},"rankscore":0.94231,"score":0.834},"mvp":{"rankscore":0.91443,"score":[0.915289440614,0.915289440614,0.915289440614,0.915289440614,0.915289440614,0.915289440614,0.915289440614,0.915289440614]},"phactboost":{"rankscore":0.98427,"score":0.999866046209465},"phastcons":{"100way_vertebrate":{"rankscore":0.71638,"score":1.0},"17way_primate":{"rankscore":0.64315,"score":0.989},"470way_mammalian":{"rankscore":0.68203,"score":1.0}},"phylop":{"100way_vertebrate":{"rankscore":0.80644,"score":7.514},"17way_primate":{"rankscore":0.4025,"score":0.599},"470way_mammalian":{"rankscore":0.61989,"score":7.613}},"polyphen2":{"hdiv":{"pred":["D","D","D","D","D"],"rankscore":0.90584,"score":[1.0,1.0,1.0,1.0,1.0]},"hvar":{"pred":["D","D","D","D","D"],"rankscore":0.97372,"score":[1.0,1.0,0.999,0.999,1.0]}},"primateai":{"pred":"D","rankscore":0.92404,"score":0.868847668171},"provean":{"converted_rankscore":0.93257,"pred":["D","D","D","D","N","D","D","D"],"score":[-6.89,-6.61,-6.37,-6.89,-1.78,-6.89,-6.59,-6.63]},"ref":"C","reliability_index":10,"revel":{"rankscore":0.99091,"score":[0.951,0.951,0.951,0.951,0.951,0.951,0.951,0.951]},"sift":{"converted_rankscore":0.91255,"pred":["D","D","D","D","D","D","D","D"],"score":[0.0,0.0,0.0,0.0,0.003,0.0,0.0,0.0]},"sift4g":{"converted_rankscore":0.92824,"pred":["D","D","D","D","D","D","D","D"],"score":[0.0,0.001,0.001,0.001,0.001,0.001,0.0,0.0]},"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":0.92676,"score":0.8672443},"er_loo":{"rankscore":0.92676,"score":0.8672443},"r":{"rankscore":0.91014,"score":0.89583844},"r_loo":{"rankscore":0.91015,"score":0.89583844}},"vep_canonical":"YES","vest4":{"rankscore":0.99725,"score":[0.984,0.981,0.98,0.988,0.982,0.983,0.99,0.98]},"vindijia_neandertal":["C","C"]},"hg38":{"end":25891733,"start":25891733},"observed":true,"snpeff":{"_license":"http://bit.ly/2suyRKt","ann":[{"cdna":{"length":"3633","position":"2400"},"cds":{"length":"2313","position":"2200"},"effect":"missense_variant","feature_id":"NM_000484.3","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.2200G>C","hgvs_p":"p.Gly734Arg","protein":{"length":"770","position":"734"},"putative_impact":"MODERATE","rank":"17","total":"18","transcript_biotype":"protein_coding"},{"cdna":{"length":"3557","position":"2324"},"cds":{"length":"2241","position":"2128"},"effect":"missense_variant","feature_id":"NM_001136016.3","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.2128G>C","hgvs_p":"p.Gly710Arg","protein":{"length":"746","position":"710"},"putative_impact":"MODERATE","rank":"16","total":"17","transcript_biotype":"protein_coding"},{"cdna":{"length":"3240","position":"2007"},"cds":{"length":"1920","position":"1807"},"effect":"missense_variant","feature_id":"NM_001136129.2","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.1807G>C","hgvs_p":"p.Gly603Arg","protein":{"length":"639","position":"603"},"putative_impact":"MODERATE","rank":"14","total":"15","transcript_biotype":"protein_coding"},{"cdna":{"length":"3465","position":"2232"},"cds":{"length":"2145","position":"2032"},"effect":"missense_variant","feature_id":"NM_001136130.2","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.2032G>C","hgvs_p":"p.Gly678Arg","protein":{"length":"714","position":"678"},"putative_impact":"MODERATE","rank":"16","total":"17","transcript_biotype":"protein_coding"},{"cdna":{"length":"3579","position":"2346"},"cds":{"length":"2259","position":"2146"},"effect":"missense_variant","feature_id":"NM_001204301.1","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.2146G>C","hgvs_p":"p.Gly716Arg","protein":{"length":"752","position":"716"},"putative_impact":"MODERATE","rank":"16","total":"17","transcript_biotype":"protein_coding"},{"cdna":{"length":"3522","position":"2289"},"cds":{"length":"2202","position":"2089"},"effect":"missense_variant","feature_id":"NM_001204302.1","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.2089G>C","hgvs_p":"p.Gly697Arg","protein":{"length":"733","position":"697"},"putative_impact":"MODERATE","rank":"15","total":"16","transcript_biotype":"protein_coding"},{"cdna":{"length":"3354","position":"2121"},"cds":{"length":"2034","position":"1921"},"effect":"missense_variant","feature_id":"NM_001204303.1","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.1921G>C","hgvs_p":"p.Gly641Arg","protein":{"length":"677","position":"641"},"putative_impact":"MODERATE","rank":"14","total":"15","transcript_biotype":"protein_coding"},{"cdna":{"length":"3576","position":"2343"},"cds":{"length":"2256","position":"2143"},"effect":"missense_variant","feature_id":"NM_201413.2","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.2143G>C","hgvs_p":"p.Gly715Arg","protein":{"length":"751","position":"715"},"putative_impact":"MODERATE","rank":"16","total":"17","transcript_biotype":"protein_coding"},{"cdna":{"length":"3408","position":"2175"},"cds":{"length":"2088","position":"1975"},"effect":"missense_variant","feature_id":"NM_201414.2","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.1975G>C","hgvs_p":"p.Gly659Arg","protein":{"length":"695","position":"659"},"putative_impact":"MODERATE","rank":"15","total":"16","transcript_biotype":"protein_coding"},{"cdna":{"length":"3295","position":"2062"},"cds":{"length":"1983","position":"1870"},"effect":"missense_variant","feature_id":"NM_001136131.2","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.1870G>C","hgvs_p":"p.Gly624Arg","protein":{"length":"660","position":"624"},"putative_impact":"MODERATE","rank":"15","total":"16","transcript_biotype":"protein_coding"}]},"vcf":{"alt":"G","position":"25891733","ref":"C"}}