{"_id":"chr21:g.25891747G>C","_version":1,"chrom":"21","clingen":{"caid":"CA409805467"},"dbnsfp":{"_license":"http://bit.ly/2VLnQBz","aa":{"alt":"R","codon_degeneracy":[0,0,0,0,0,0,0,0],"codonpos":[2,2,2,2,2,2,2,2],"pos":[729,598,654,710,619,705,673,711],"ref":"T","refcodon":["ACA","ACA","ACA","ACA","ACA","ACA","ACA","ACA"]},"alphamissense":{"pred":["A","A","A","A","A","B","A","A"],"rankscore":0.65907,"score":[0.4651,0.3627,0.464,0.4853,0.5297,0.311,0.4875,0.3962]},"alt":"C","altai_neandertal":["G","G"],"ancestral_allele":"G","appris":["principal4","alternative1","alternative1","alternative1"],"bayesdel":{"add_af":{"pred":"D","rankscore":0.92264,"score":0.445223},"no_af":{"pred":"D","rankscore":0.92169,"score":0.401756}},"bstatistic":{"converted_rankscore":0.013,"score":993.0},"cadd":{"phred":26.5,"raw_rankscore":0.76313,"raw_score":4.735629},"chagyrskaya_neandertal":["G","G"],"chrom":"21","clinpred":{"pred":"D","rankscore":0.55574,"score":0.902711868286133},"dann":{"rankscore":0.50148,"score":0.990006137077453},"denisova":["G","G"],"deogen2":{"pred":"D","rankscore":0.91011,"score":0.69088},"eigen":{"phred_coding":6.276209,"raw_coding":0.63294091226708,"raw_coding_rankscore":0.7527},"eigen-pc":{"phred_coding":8.112616,"raw_coding":0.718457277025247,"raw_coding_rankscore":0.83782},"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":0.9682,"score":[-13.726,-15.451,-14.133,-12.891,-13.027,-13.182]},"eve":{"class10_pred":"U","class20_pred":"U","class25_pred":"U","class30_pred":"U","class40_pred":"U","class50_pred":"B","class60_pred":"B","class70_pred":"B","class75_pred":"B","class80_pred":"B","class90_pred":"B","rankscore":0.32432,"score":0.2394454252234483},"fathmm":{"converted_rankscore":0.95561,"pred":["D","D","D","D","D","D","D"],"score":[-3.76,-3.76,-3.76,-3.76,-3.76,-3.76,-3.76]},"fathmm-mkl":{"coding_group":"AEFBI","coding_pred":"D","coding_rankscore":0.97447,"coding_score":0.9956},"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":0.999999999999962},"gerp":{"91_mammals":{"rankscore":0.41487,"score":2.16}},"gerp++":{"nr":5.65,"rs":5.65,"rs_rankscore":0.86881},"gmvp":{"rankscore":0.9325,"score":0.9327101123157309},"hg18":{"end":26185930,"start":26185930},"hg19":{"end":27264059,"start":27264059},"hg38":{"end":25891747,"start":25891747},"hgvsc":["c.2186C>G","c.1793C>G","c.2129C>G","c.2114C>G","c.2018C>G","c.1961C>G","c.1856C>G","c.2132C>G"],"hgvsp":["p.T711R","p.Thr598Arg","p.Thr673Arg","p.Thr705Arg","p.T705R","p.Thr654Arg","p.T729R","p.T710R","p.T673R","p.Thr711Arg","p.Thr729Arg","p.Thr710Arg","p.Thr619Arg","p.T619R","p.T654R","p.T598R"],"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":0.80823,"score":[0.949405,0.949405,0.949405,0.949405,0.949405,0.949405,0.949405,0.950005]},"lrt":{"converted_rankscore":0.8433,"omega":0.0,"pred":"D","score":0.0},"m-cap":{"pred":"D","rankscore":0.89615,"score":0.263887},"metalr":{"pred":"D","rankscore":0.93712,"score":0.8135},"metarnn":{"pred":["D","D","D","D","D","D","D","D"],"rankscore":0.72756,"score":[0.70624715,0.70624715,0.70624715,0.70624715,0.70624715,0.70624715,0.70624727,0.70624727]},"metasvm":{"pred":"D","rankscore":0.95932,"score":0.9182},"mpc":{"rankscore":0.82515,"score":1.28073235823},"mutationassessor":{"pred":"N","rankscore":0.02229,"score":-0.6},"mutationtaster":{"aae":["T729R","T598R","T654R","T710R","T673R","T711R","T673R","T705R","T619R"],"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":0.95743,"score":0.9820065},"mutpred":{"aa_change":"T729R","accession":"P05067","pred":{"mechanism":"Gain of MoRF binding","p_val":0.0065},"rankscore":0.60693,"score":0.51},"mvp":{"rankscore":0.93246,"score":[0.933144490681,0.933144490681,0.933144490681,0.933144490681,0.933144490681,0.933144490681,0.933144490681,0.933144490681]},"phactboost":{"rankscore":0.87837,"score":0.988617078898991},"phastcons":{"100way_vertebrate":{"rankscore":0.71638,"score":1.0},"17way_primate":{"rankscore":0.69303,"score":0.993},"470way_mammalian":{"rankscore":0.68203,"score":1.0}},"phylop":{"100way_vertebrate":{"rankscore":0.82948,"score":7.672},"17way_primate":{"rankscore":0.7674,"score":0.676},"470way_mammalian":{"rankscore":0.95134,"score":11.738}},"polyphen2":{"hdiv":{"pred":["D","D","D","D","D"],"rankscore":0.90584,"score":[1.0,1.0,0.997,0.997,1.0]},"hvar":{"pred":["D","D","D","D","D"],"rankscore":0.92359,"score":[0.999,0.999,0.991,0.991,0.999]}},"primateai":{"pred":"T","rankscore":0.76796,"score":0.765812635422},"provean":{"converted_rankscore":0.42001,"pred":["N","N","N","N","N","N","N"],"score":[-1.64,-1.44,-1.26,-1.64,-1.64,-1.64,-1.78]},"ref":"G","reliability_index":10,"revel":{"rankscore":0.9171,"score":[0.757,0.757,0.757,0.757,0.757,0.757,0.757,0.757]},"sift":{"converted_rankscore":0.44694,"pred":["D","D","D","D","D","D","T"],"score":[0.032,0.036,0.036,0.034,0.038,0.039,0.23]},"sift4g":{"converted_rankscore":0.63109,"pred":["D","D","D","D","T","D","D","D"],"score":[0.014,0.035,0.033,0.013,0.081,0.028,0.015,0.014]},"siphy_29way":{"logodds_rankscore":0.95998,"logodds_score":19.6915,"pi":{"a":0.0,"c":0.0,"g":1.0,"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":0.65775,"score":0.41711512},"er_loo":{"rankscore":0.65775,"score":0.41711512},"r":{"rankscore":0.56414,"score":0.34168994},"r_loo":{"rankscore":0.56414,"score":0.34168994}},"vep_canonical":"YES","vest4":{"rankscore":0.77226,"score":[0.747,0.727,0.747,0.724,0.727,0.775,0.723,0.736]},"vindijia_neandertal":["G","G"]},"hg38":{"end":25891747,"start":25891747},"observed":true,"snpeff":{"_license":"http://bit.ly/2suyRKt","ann":[{"cdna":{"length":"3633","position":"2386"},"cds":{"length":"2313","position":"2186"},"effect":"missense_variant","feature_id":"NM_000484.3","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.2186C>G","hgvs_p":"p.Thr729Arg","protein":{"length":"770","position":"729"},"putative_impact":"MODERATE","rank":"17","total":"18","transcript_biotype":"protein_coding"},{"cdna":{"length":"3557","position":"2310"},"cds":{"length":"2241","position":"2114"},"effect":"missense_variant","feature_id":"NM_001136016.3","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.2114C>G","hgvs_p":"p.Thr705Arg","protein":{"length":"746","position":"705"},"putative_impact":"MODERATE","rank":"16","total":"17","transcript_biotype":"protein_coding"},{"cdna":{"length":"3240","position":"1993"},"cds":{"length":"1920","position":"1793"},"effect":"missense_variant","feature_id":"NM_001136129.2","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.1793C>G","hgvs_p":"p.Thr598Arg","protein":{"length":"639","position":"598"},"putative_impact":"MODERATE","rank":"14","total":"15","transcript_biotype":"protein_coding"},{"cdna":{"length":"3465","position":"2218"},"cds":{"length":"2145","position":"2018"},"effect":"missense_variant","feature_id":"NM_001136130.2","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.2018C>G","hgvs_p":"p.Thr673Arg","protein":{"length":"714","position":"673"},"putative_impact":"MODERATE","rank":"16","total":"17","transcript_biotype":"protein_coding"},{"cdna":{"length":"3579","position":"2332"},"cds":{"length":"2259","position":"2132"},"effect":"missense_variant","feature_id":"NM_001204301.1","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.2132C>G","hgvs_p":"p.Thr711Arg","protein":{"length":"752","position":"711"},"putative_impact":"MODERATE","rank":"16","total":"17","transcript_biotype":"protein_coding"},{"cdna":{"length":"3522","position":"2275"},"cds":{"length":"2202","position":"2075"},"effect":"missense_variant","feature_id":"NM_001204302.1","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.2075C>G","hgvs_p":"p.Thr692Arg","protein":{"length":"733","position":"692"},"putative_impact":"MODERATE","rank":"15","total":"16","transcript_biotype":"protein_coding"},{"cdna":{"length":"3354","position":"2107"},"cds":{"length":"2034","position":"1907"},"effect":"missense_variant","feature_id":"NM_001204303.1","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.1907C>G","hgvs_p":"p.Thr636Arg","protein":{"length":"677","position":"636"},"putative_impact":"MODERATE","rank":"14","total":"15","transcript_biotype":"protein_coding"},{"cdna":{"length":"3576","position":"2329"},"cds":{"length":"2256","position":"2129"},"effect":"missense_variant","feature_id":"NM_201413.2","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.2129C>G","hgvs_p":"p.Thr710Arg","protein":{"length":"751","position":"710"},"putative_impact":"MODERATE","rank":"16","total":"17","transcript_biotype":"protein_coding"},{"cdna":{"length":"3408","position":"2161"},"cds":{"length":"2088","position":"1961"},"effect":"missense_variant","feature_id":"NM_201414.2","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.1961C>G","hgvs_p":"p.Thr654Arg","protein":{"length":"695","position":"654"},"putative_impact":"MODERATE","rank":"15","total":"16","transcript_biotype":"protein_coding"},{"cdna":{"length":"3295","position":"2048"},"cds":{"length":"1983","position":"1856"},"effect":"missense_variant","feature_id":"NM_001136131.2","feature_type":"transcript","gene_id":"APP","genename":"APP","hgvs_c":"c.1856C>G","hgvs_p":"p.Thr619Arg","protein":{"length":"660","position":"619"},"putative_impact":"MODERATE","rank":"15","total":"16","transcript_biotype":"protein_coding"},{"effect":"sequence_feature","feature_id":"NM_000484.3","feature_type":"modified-residue:Phosphothreonine","gene_id":"APP","genename":"APP","hgvs_c":"c.2186C>G","putative_impact":"MODERATE","rank":"17","total":"18","transcript_biotype":"protein_coding"},{"effect":"sequence_feature","feature_id":"NM_001136016.3","feature_type":"modified-residue:Phosphothreonine","gene_id":"APP","genename":"APP","hgvs_c":"c.2114C>G","putative_impact":"MODERATE","rank":"16","total":"17","transcript_biotype":"protein_coding"},{"effect":"sequence_feature","feature_id":"NM_001136129.2","feature_type":"modified-residue:Phosphothreonine","gene_id":"APP","genename":"APP","hgvs_c":"c.1793C>G","putative_impact":"MODERATE","rank":"14","total":"15","transcript_biotype":"protein_coding"},{"effect":"sequence_feature","feature_id":"NM_001204301.1","feature_type":"modified-residue:Phosphothreonine","gene_id":"APP","genename":"APP","hgvs_c":"c.2132C>G","putative_impact":"MODERATE","rank":"16","total":"17","transcript_biotype":"protein_coding"},{"effect":"sequence_feature","feature_id":"NM_001204302.1","feature_type":"modified-residue:Phosphothreonine","gene_id":"APP","genename":"APP","hgvs_c":"c.2075C>G","putative_impact":"MODERATE","rank":"15","total":"16","transcript_biotype":"protein_coding"},{"effect":"sequence_feature","feature_id":"NM_001204303.1","feature_type":"modified-residue:Phosphothreonine","gene_id":"APP","genename":"APP","hgvs_c":"c.1907C>G","putative_impact":"MODERATE","rank":"14","total":"15","transcript_biotype":"protein_coding"}]},"vcf":{"alt":"C","position":"25891747","ref":"G"}}