{"_id":"chr21:g.25891732C>T","_version":1,"chrom":"21","clingen":{"caid":"CA409805432"},"dbnsfp":{"_license":"http://bit.ly/2VLnQBz","aa":{"alt":"D","codon_degeneracy":[0,0,0,0,0,0,0,0],"codonpos":[2,2,2,2,2,2,2,2],"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":0.942,"score":[0.9653,0.9878,0.9835,0.9912,0.9918,0.9704,0.9861,0.9743]},"alt":"T","altai_neandertal":["C","C"],"ancestral_allele":"C","appris":["principal4","alternative1","alternative1","alternative1"],"bayesdel":{"add_af":{"pred":"D","rankscore":0.95351,"score":0.53743},"no_af":{"pred":"D","rankscore":0.95282,"score":0.534205}},"bstatistic":{"converted_rankscore":0.013,"score":993.0},"cadd":{"phred":27.1,"raw_rankscore":0.79298,"raw_score":4.851518},"chagyrskaya_neandertal":["C","C"],"chrom":"21","clinpred":{"pred":"D","rankscore":0.88657,"score":0.996098279953003},"dann":{"rankscore":0.91972,"score":0.9983863170545298},"denisova":["C","C"],"deogen2":{"pred":"D","rankscore":0.95199,"score":0.808779},"eigen":{"phred_coding":11.07192,"raw_coding":0.900855351442321,"raw_coding_rankscore":0.91799},"eigen-pc":{"phred_coding":12.44204,"raw_coding":0.867841751273441,"raw_coding_rankscore":0.94015},"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":0.83441,"score":[-10.9,-11.44,-11.716,-11.511,-11.1,-11.294]},"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":0.82775,"score":0.7456548889063628},"fathmm":{"converted_rankscore":0.97606,"pred":["D","D","D","D","D","D","D","D"],"score":[-4.48,-4.48,-4.48,-4.48,-4.0,-4.48,-4.48,-4.48]},"fathmm-mkl":{"coding_group":"AEFBI","coding_pred":"D","coding_rankscore":0.90377,"coding_score":0.99042},"fathmm-xf":{"coding_pred":"D","coding_rankscore":0.91665,"coding_score":0.930011},"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++":{"nr":5.65,"rs":5.65,"rs_rankscore":0.86881},"gmvp":{"rankscore":0.99467,"score":0.9947045552626518},"hg18":{"end":26185915,"start":26185915},"hg19":{"end":27264044,"start":27264044},"hg38":{"end":25891732,"start":25891732},"hgvsc":["c.2144G>A","c.2033G>A","c.2129G>A","c.2201G>A","c.1976G>A","c.1808G>A","c.1871G>A","c.2147G>A"],"hgvsp":["p.G710D","p.G716D","p.Gly734Asp","p.G603D","p.Gly715Asp","p.G715D","p.Gly659Asp","p.Gly710Asp","p.Gly716Asp","p.G659D","p.G678D","p.G734D","p.Gly624Asp","p.G624D","p.Gly678Asp","p.Gly603Asp"],"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":0.97602,"score":[0.992601,0.990234,0.990234,0.992601,0.990234,0.992601,0.992601,0.990234]},"lrt":{"converted_rankscore":0.8433,"omega":0.0,"pred":"D","score":0.0},"m-cap":{"pred":"D","rankscore":0.94783,"score":0.477367},"metalr":{"pred":"D","rankscore":0.98379,"score":0.9502},"metarnn":{"pred":["D","D","D","D","D","D","D","D"],"rankscore":0.94004,"score":[0.9467686,0.9467686,0.9467686,0.9467686,0.9467686,0.9467686,0.9467686,0.9467686]},"metasvm":{"pred":"D","rankscore":0.99172,"score":1.0883},"mpc":{"rankscore":0.85234,"score":1.40245125629},"mutationassessor":{"pred":"M","rankscore":0.53209,"score":1.965},"mutationtaster":{"aae":["G734D","G603D","G659D","G715D","G678D","G716D","G678D","G710D","G624D"],"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":0.9756,"score":0.9944528},"mutpred":{"aa_change":"G734D","accession":"P05067","pred":{"mechanism":"Loss of catalytic residue at V735","p_val":0.0961},"rankscore":0.93127,"score":0.817},"mvp":{"rankscore":0.94971,"score":[0.95023243647,0.95023243647,0.95023243647,0.95023243647,0.95023243647,0.95023243647,0.95023243647,0.95023243647]},"phactboost":{"rankscore":0.9795,"score":0.999784749932061},"phastcons":{"100way_vertebrate":{"rankscore":0.71638,"score":1.0},"17way_primate":{"rankscore":0.62547,"score":0.987},"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":[1.0,1.0,0.998,0.998,1.0]}},"primateai":{"pred":"D","rankscore":0.92863,"score":0.872064828873},"provean":{"converted_rankscore":0.89833,"pred":["D","D","D","D","N","D","D","D"],"score":[-6.06,-5.93,-5.71,-6.06,-1.38,-6.06,-5.79,-5.83]},"ref":"C","reliability_index":10,"revel":{"rankscore":0.98921,"score":[0.946,0.946,0.946,0.946,0.946,0.946,0.946,0.946]},"sift":{"converted_rankscore":0.91255,"pred":["D","D","D","D","D","D","D","D"],"score":[0.0,0.0,0.0,0.0,0.004,0.0,0.0,0.0]},"sift4g":{"converted_rankscore":0.92824,"pred":["D","D","D","D","D","D","D","D"],"score":[0.0,0.001,0.001,0.001,0.001,0.001,0.001,0.0]},"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":0.95803,"score":0.91160464},"er_loo":{"rankscore":0.95804,"score":0.91160464},"r":{"rankscore":0.93528,"score":0.9228738},"r_loo":{"rankscore":0.93529,"score":0.9228738}},"vep_canonical":"YES","vest4":{"rankscore":0.9967,"score":[0.968,0.978,0.973,0.989,0.977,0.988,0.981,0.966]},"vindijia_neandertal":["C","C"]},"hg38":{"end":25891732,"start":25891732},"observed":true,"snpeff":{"_license":"http://bit.ly/2suyRKt","ann":[{"cdna":{"length":"3633","position":"2401"},"cds":{"length":"2313","position":"2201"},"effect":"missense_variant","feature_id":"NM_000484.3","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.2201G>A","hgvs_p":"p.Gly734Asp","protein":{"length":"770","position":"734"},"putative_impact":"MODERATE","rank":"17","total":"18","transcript_biotype":"protein_coding"},{"cdna":{"length":"3557","position":"2325"},"cds":{"length":"2241","position":"2129"},"effect":"missense_variant","feature_id":"NM_001136016.3","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.2129G>A","hgvs_p":"p.Gly710Asp","protein":{"length":"746","position":"710"},"putative_impact":"MODERATE","rank":"16","total":"17","transcript_biotype":"protein_coding"},{"cdna":{"length":"3240","position":"2008"},"cds":{"length":"1920","position":"1808"},"effect":"missense_variant","feature_id":"NM_001136129.2","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.1808G>A","hgvs_p":"p.Gly603Asp","protein":{"length":"639","position":"603"},"putative_impact":"MODERATE","rank":"14","total":"15","transcript_biotype":"protein_coding"},{"cdna":{"length":"3465","position":"2233"},"cds":{"length":"2145","position":"2033"},"effect":"missense_variant","feature_id":"NM_001136130.2","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.2033G>A","hgvs_p":"p.Gly678Asp","protein":{"length":"714","position":"678"},"putative_impact":"MODERATE","rank":"16","total":"17","transcript_biotype":"protein_coding"},{"cdna":{"length":"3579","position":"2347"},"cds":{"length":"2259","position":"2147"},"effect":"missense_variant","feature_id":"NM_001204301.1","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.2147G>A","hgvs_p":"p.Gly716Asp","protein":{"length":"752","position":"716"},"putative_impact":"MODERATE","rank":"16","total":"17","transcript_biotype":"protein_coding"},{"cdna":{"length":"3522","position":"2290"},"cds":{"length":"2202","position":"2090"},"effect":"missense_variant","feature_id":"NM_001204302.1","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.2090G>A","hgvs_p":"p.Gly697Asp","protein":{"length":"733","position":"697"},"putative_impact":"MODERATE","rank":"15","total":"16","transcript_biotype":"protein_coding"},{"cdna":{"length":"3354","position":"2122"},"cds":{"length":"2034","position":"1922"},"effect":"missense_variant","feature_id":"NM_001204303.1","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.1922G>A","hgvs_p":"p.Gly641Asp","protein":{"length":"677","position":"641"},"putative_impact":"MODERATE","rank":"14","total":"15","transcript_biotype":"protein_coding"},{"cdna":{"length":"3576","position":"2344"},"cds":{"length":"2256","position":"2144"},"effect":"missense_variant","feature_id":"NM_201413.2","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.2144G>A","hgvs_p":"p.Gly715Asp","protein":{"length":"751","position":"715"},"putative_impact":"MODERATE","rank":"16","total":"17","transcript_biotype":"protein_coding"},{"cdna":{"length":"3408","position":"2176"},"cds":{"length":"2088","position":"1976"},"effect":"missense_variant","feature_id":"NM_201414.2","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.1976G>A","hgvs_p":"p.Gly659Asp","protein":{"length":"695","position":"659"},"putative_impact":"MODERATE","rank":"15","total":"16","transcript_biotype":"protein_coding"},{"cdna":{"length":"3295","position":"2063"},"cds":{"length":"1983","position":"1871"},"effect":"missense_variant","feature_id":"NM_001136131.2","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.1871G>A","hgvs_p":"p.Gly624Asp","protein":{"length":"660","position":"624"},"putative_impact":"MODERATE","rank":"15","total":"16","transcript_biotype":"protein_coding"}]},"vcf":{"alt":"T","position":"25891732","ref":"C"}}