{"_id":"chr21:g.27264038A>T","_version":1,"cadd":{"_license":"http://bit.ly/2TIuab9","alt":"T","anc":"A","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":0.03,"dna":{"helt":0.95,"mgw":0.73,"prot":-3.93,"roll":6.88},"dst2splice":5,"dst2spltype":"DONOR","encode":{"exp":8855.84,"h3k27ac":4.04,"h3k4me1":9.0,"h3k4me3":3.0,"nucleo":1.1},"exon":"17/18","fitcons":0.701516,"gc":0.42,"gene":{"ccds_id":"CCDS13576.1","cds":{"cdna_pos":2241,"cds_pos":2207,"rel_cdna_pos":0.65,"rel_cds_pos":0.95},"feature_id":"ENST00000346798","gene_id":"ENSG00000142192","genename":"APP","prot":{"domain":"ndomain","protpos":736,"rel_prot_pos":0.96}},"gerp":{"n":5.65,"rs":659.2,"rs_pval":2.97824e-172,"s":5.65},"grantham":121,"isderived":"TRUE","isknownvariant":"FALSE","istv":"TRUE","length":0,"mapability":{"20bp":1,"35bp":1},"min_dist_tse":73,"min_dist_tss":6258,"mutindex":-28,"naa":"E","oaa":"V","phast_cons":{"mammalian":1.0,"primate":0.911,"vertebrate":1.0},"phred":34,"phylop":{"mammalian":2.276,"primate":0.53,"vertebrate":4.743},"polyphen":{"cat":"probably_damaging","val":0.978},"pos":27264038,"rawscore":7.298463,"ref":"A","segway":"R1","sift":{"cat":"deleterious","val":0},"type":"SNV"},"chrom":"21","dbnsfp":{"_license":"http://bit.ly/2VLnQBz","aa":{"alt":"E","codon_degeneracy":[0,0,0,0,0,0,0,0],"codonpos":[2,2,2,2,2,2,2,2],"pos":[736,605,661,717,626,712,680,718],"ref":"V","refcodon":["GTG","GTG","GTG","GTG","GTG","GTG","GTG","GTG"]},"alphamissense":{"pred":["P","P","P","P","P","P","P","P"],"rankscore":0.9186,"score":[0.9523,0.9702,0.9561,0.9747,0.9834,0.9527,0.9723,0.9496]},"alt":"T","altai_neandertal":["A","A"],"ancestral_allele":"A","appris":["principal4","alternative1","alternative1","alternative1"],"bayesdel":{"add_af":{"pred":"D","rankscore":0.95496,"score":0.542053},"no_af":{"pred":"D","rankscore":0.95429,"score":0.540845}},"bstatistic":{"converted_rankscore":0.013,"score":993.0},"chagyrskaya_neandertal":["A","A"],"chrom":"21","clinpred":{"pred":"D","rankscore":0.89565,"score":0.996548354625702},"dann":{"rankscore":0.55083,"score":0.9919494508036282},"denisova":["A","A"],"deogen2":{"pred":"D","rankscore":0.94777,"score":0.796831},"eigen":{"phred_coding":8.938669,"raw_coding":0.807985455663106,"raw_coding_rankscore":0.86604},"eigen-pc":{"phred_coding":10.03993,"raw_coding":0.797148454038886,"raw_coding_rankscore":0.89593},"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":0.95917,"score":[-14.627,-15.028,-14.703,-14.834,-14.89,-14.731]},"eve":{"class10_pred":"U","class20_pred":"U","class25_pred":"U","class30_pred":"U","class40_pred":"U","class50_pred":"U","class60_pred":"U","class70_pred":"B","class75_pred":"B","class80_pred":"B","class90_pred":"B","rankscore":0.43109,"score":0.3331061776211377},"fathmm":{"converted_rankscore":0.97849,"pred":["D","D","D","D","D","D","D"],"score":[-4.6,-4.6,-4.6,-4.6,-4.6,-4.6,-4.6]},"fathmm-mkl":{"coding_group":"AEFBI","coding_pred":"D","coding_rankscore":0.9502,"coding_score":0.99361},"fathmm-xf":{"coding_pred":"D","coding_rankscore":0.95702,"coding_score":0.946971},"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":0.99999999994553},"gerp++":{"nr":5.65,"rs":5.65,"rs_rankscore":0.86881},"gmvp":{"rankscore":0.95205,"score":0.9522163557309385},"hg18":{"end":26185909,"start":26185909},"hg19":{"end":27264038,"start":27264038},"hg38":{"end":25891726,"start":25891726},"hgvsc":["c.2207T>A","c.2039T>A","c.1814T>A","c.2135T>A","c.2150T>A","c.2153T>A","c.1982T>A","c.1877T>A"],"hgvsp":["p.Val605Glu","p.V626E","p.V718E","p.Val626Glu","p.Val712Glu","p.V736E","p.Val717Glu","p.Val680Glu","p.Val661Glu","p.V717E","p.V605E","p.Val718Glu","p.V712E","p.V680E","p.Val736Glu","p.V661E"],"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":0.94842,"score":[0.985051,0.985051,0.985051,0.985051,0.985051,0.985051,0.985051,0.985051]},"lrt":{"converted_rankscore":0.8433,"omega":0.055622,"pred":"D","score":1e-6},"m-cap":{"pred":"D","rankscore":0.97208,"score":0.666419},"metalr":{"pred":"D","rankscore":0.98307,"score":0.9481},"metarnn":{"pred":["D","D","D","D","D","D","D","D"],"rankscore":0.93803,"score":[0.94479024,0.94479024,0.94479024,0.94479024,0.94479024,0.94479024,0.9447903,0.9447903]},"metasvm":{"pred":"D","rankscore":0.99736,"score":1.1019},"mpc":{"rankscore":0.88064,"score":1.5630790888},"mutationassessor":{"pred":"L","rankscore":0.50365,"score":1.895},"mutationtaster":{"aae":["V736E","V605E","V661E","V717E","V680E","V718E","V680E","V712E","V626E"],"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":0.97861,"score":0.995698},"mutpred":{"aa_change":"V736E","accession":"P05067","pred":{"mechanism":"Gain of disorder","p_val":0.0028},"rankscore":0.86892,"score":0.736},"mvp":{"rankscore":0.99845,"score":[0.998464005098,0.998464005098,0.998464005098,0.998464005098,0.998464005098,0.998464005098,0.998464005098,0.998464005098]},"phactboost":{"rankscore":0.93253,"score":0.99755532736305},"phastcons":{"100way_vertebrate":{"rankscore":0.71638,"score":1.0},"17way_primate":{"rankscore":0.54974,"score":0.972},"470way_mammalian":{"rankscore":0.68203,"score":1.0}},"phylop":{"100way_vertebrate":{"rankscore":0.92042,"score":8.881},"17way_primate":{"rankscore":0.94297,"score":0.756},"470way_mammalian":{"rankscore":0.86698,"score":11.127}},"polyphen2":{"hdiv":{"pred":["D","D","D","D","D"],"rankscore":0.77913,"score":[0.999,0.999,0.994,0.994,0.999]},"hvar":{"pred":["D","D","P","P","D"],"rankscore":0.78396,"score":[0.989,0.966,0.827,0.827,0.989]}},"primateai":{"pred":"T","rankscore":0.68051,"score":0.706256151199},"provean":{"converted_rankscore":0.84882,"pred":["D","D","D","D","D","D","D"],"score":[-5.37,-5.26,-5.07,-5.37,-5.37,-5.14,-5.37]},"ref":"A","reliability_index":10,"revel":{"rankscore":0.9974,"score":[0.974,0.974,0.974,0.974,0.974,0.974,0.974,0.974]},"sift":{"converted_rankscore":0.91255,"pred":["D","D","D","D","D","D","D"],"score":[0.0,0.0,0.0,0.0,0.0,0.0,0.0]},"sift4g":{"converted_rankscore":0.92824,"pred":["D","D","D","D","D","D","D","D"],"score":[0.0,0.0,0.0,0.0,0.0,0.0,0.0,0.0]},"siphy_29way":{"logodds_rankscore":0.78608,"logodds_score":15.8391,"pi":{"a":1.0,"c":0.0,"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":0.97564,"score":0.9369286},"er_loo":{"rankscore":0.97565,"score":0.9369286},"r":{"rankscore":0.94509,"score":0.9327107},"r_loo":{"rankscore":0.9451,"score":0.9327107}},"vep_canonical":"YES","vest4":{"rankscore":0.91736,"score":[0.914,0.912,0.913,0.908,0.912,0.915,0.914,0.914]},"vindijia_neandertal":["A","A"]},"hg19":{"end":27264038,"start":27264038},"snpeff":{"_license":"http://bit.ly/2suyRKt","ann":[{"cdna":{"length":"3633","position":"2407"},"cds":{"length":"2313","position":"2207"},"effect":"missense_variant","feature_id":"NM_000484.3","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.2207T>A","hgvs_p":"p.Val736Glu","protein":{"length":"770","position":"736"},"putative_impact":"MODERATE","rank":"17","total":"18","transcript_biotype":"protein_coding"},{"cdna":{"length":"3557","position":"2331"},"cds":{"length":"2241","position":"2135"},"effect":"missense_variant","feature_id":"NM_001136016.3","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.2135T>A","hgvs_p":"p.Val712Glu","protein":{"length":"746","position":"712"},"putative_impact":"MODERATE","rank":"16","total":"17","transcript_biotype":"protein_coding"},{"cdna":{"length":"3240","position":"2014"},"cds":{"length":"1920","position":"1814"},"effect":"missense_variant","feature_id":"NM_001136129.2","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.1814T>A","hgvs_p":"p.Val605Glu","protein":{"length":"639","position":"605"},"putative_impact":"MODERATE","rank":"14","total":"15","transcript_biotype":"protein_coding"},{"cdna":{"length":"3465","position":"2239"},"cds":{"length":"2145","position":"2039"},"effect":"missense_variant","feature_id":"NM_001136130.2","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.2039T>A","hgvs_p":"p.Val680Glu","protein":{"length":"714","position":"680"},"putative_impact":"MODERATE","rank":"16","total":"17","transcript_biotype":"protein_coding"},{"cdna":{"length":"3579","position":"2353"},"cds":{"length":"2259","position":"2153"},"effect":"missense_variant","feature_id":"NM_001204301.1","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.2153T>A","hgvs_p":"p.Val718Glu","protein":{"length":"752","position":"718"},"putative_impact":"MODERATE","rank":"16","total":"17","transcript_biotype":"protein_coding"},{"cdna":{"length":"3522","position":"2296"},"cds":{"length":"2202","position":"2096"},"effect":"missense_variant","feature_id":"NM_001204302.1","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.2096T>A","hgvs_p":"p.Val699Glu","protein":{"length":"733","position":"699"},"putative_impact":"MODERATE","rank":"15","total":"16","transcript_biotype":"protein_coding"},{"cdna":{"length":"3354","position":"2128"},"cds":{"length":"2034","position":"1928"},"effect":"missense_variant","feature_id":"NM_001204303.1","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.1928T>A","hgvs_p":"p.Val643Glu","protein":{"length":"677","position":"643"},"putative_impact":"MODERATE","rank":"14","total":"15","transcript_biotype":"protein_coding"},{"cdna":{"length":"3576","position":"2350"},"cds":{"length":"2256","position":"2150"},"effect":"missense_variant","feature_id":"NM_201413.2","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.2150T>A","hgvs_p":"p.Val717Glu","protein":{"length":"751","position":"717"},"putative_impact":"MODERATE","rank":"16","total":"17","transcript_biotype":"protein_coding"},{"cdna":{"length":"3408","position":"2182"},"cds":{"length":"2088","position":"1982"},"effect":"missense_variant","feature_id":"NM_201414.2","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.1982T>A","hgvs_p":"p.Val661Glu","protein":{"length":"695","position":"661"},"putative_impact":"MODERATE","rank":"15","total":"16","transcript_biotype":"protein_coding"},{"cdna":{"length":"3295","position":"2069"},"cds":{"length":"1983","position":"1877"},"effect":"missense_variant","feature_id":"NM_001136131.2","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.1877T>A","hgvs_p":"p.Val626Glu","protein":{"length":"660","position":"626"},"putative_impact":"MODERATE","rank":"15","total":"16","transcript_biotype":"protein_coding"}]},"vcf":{"alt":"T","position":"27264038","ref":"A"}}