Jian-Min Chen Claude Férec David N

Jian-Min Chen · Claude Férec · David N. Cooper

A systematic analysis of disease-associated variants in the 3’ regulatory regions of human protein-coding genes II: the importance of mRNA secondary structure in assessing the functionality of 3' UTR variants

Online Supplementary Materials

1. Supplementary Tables

Note: gene symbols and the source of sequence for each variant are listed. Point mutations and insertion variants are indicated in red below the wild-type sequences; deletion variants are barred and highlighted in red. When a variant is annotated in the context of genomic sequence, the coding sequence of the last exon is shaded; the translational termination codon is in upper case and bold; the upstream core polyadenylation signal (UCPAS) hexamer is in bold and highlighted in blue; the vertical line in red indicates the cleavage site wherever possible to ascertain. When a variant is annotated in the context of mRNA sequence, only the translational termination codon is in upper case and bold.

Table S1 Group 1 variants

CXCL12

AY802782.1

13681 cctctgttct tgtcaacagg aggttcaaga tgTGAgaggg tcagacgcct gaggaaccct

13741 tacagtagga gcccagctct gaaaccagtg ttagggaagg gcctgccaca gcctcccctg

13801 ccagggcagg gccccaggca ttgccaaggg ctttgttttg cacactttgc catattttca

13861 ccatttgatt atgtagcaaa atacatgaca tttatttttc atttagtttg attattcagt

13921 gtcactggcg acacgtagca gcttagacta aggccattat tgtacttgcc ttattagagt

13981 gtctttccac ggagccactc ctctgactca gggctcctgg gttttgtatt ctctgagctg

14041 tgcaggtggg gagactgggc tgagggagcc tggccccatg gtcagcccta gggtggagag

14101 ccaccaagag ggacgcctgg gggtgccagg accagtcaac ctgggcaaag cctagtgaag

14161 gcttctctct gtgggatggg atggtggagg gccacatggg aggctcaccc ccttctccat

14221 ccacatggga gccgggtctg cctcttctgg gagggcagca gggctaccct gagctgaggc

gccAggtctg

14281 agcagtgtga ggccagggca gagtgagacc cagccctcat cccgagcacc tccacatcct

14341 ccacgttctg ctcatcattc tctgtctcat ccatcatcat gtgtgtccac gactgtctcc

14401 atggccccgc aaaaggactc tcaggaccaa agctttcatg taaactgtgc accaagcagg

14461 aaatgaaaat gtcttgtgtt acctgaaaac actgtgcaca tctgtgtctt gtttggaata

14521 ttgtccattg tccaatccta tgtttttgtt caaagccagc gtcctcctct gtgaccaatg

14581 tcttgatgca tgcactgttc cccctgtgca gccgctgagc gaggagatgc tccttgggcc

14641 ctttgagtgc agtcctgatc agagccgtgg tcctttgggg tgaactacct tggttccccc

14701 actgatcaca aaaacatggt gggtccatgg gcagagccca agggaattcg gtgtgcacca

14761 gggttgaccc cagaggattg ctgccccatc agtgctccct cacatgtcag taccttcaaa

14821 ctagggccaa gcccagcact gcttgaggaa aacaagcatt cacaacttgt ttttggtttt

14881 taaaacccag tccacaaaat aaccaatcct ggacatgaag attctttccc aattcacatc

14941 taacctcatc ttcttcacca tttggcaatg ccatcatctc ctgccttcct cctgggccct

15001 ctctgctctg cgtgtcacct gtgcttcggg cccttcccac aggacatttc tctaagagaa

15061 caatgtgcta tgtgaagagt aagtcaacct gcctgacatt tggagtgttc cccttccact

15121 gagggcagtc gatagagctg tattaagcca cttaaaatgt tcacttttga caaaggcaag

15181 cacttgtggg tttttgtttt gtttttcatt cagtcttacg aatacttttg ccctttgatt

15241 aaagactcca gttaaaaaaa attttaatga agaaagtgga aaacaaggaa gtcaaagcaa

15301 ggaaactatg taacatgtag gaagtaggaa gtaaattata gtgatgtaat cttgaattgt

15361 aactgttctt gaatttaata atctgtaggg taattagtaa catgtgttaa gtattttcat

15421 aagtatttca aattggagct tcatggcaga aggcaaaccc atcaacaaaa attgtccctt

15481 aaacaaaaat taaaatcctc aatccagcta tgttatattg aaaaaataga gcctgaggga

15541 tctttactag ttataaagat acagaactct ttcaaaacct tttgaaatta acctctcact

15601 ataccagtat aattgagttt tcagtggggc agtcattatc caggtaatcc aagatatttt

15661 aaaatctgtc acgtagaact tggatgtacc tgcccccaat ccatgaacca agaccattga

15721 attcttggtt gaggaaacaa acatgaccct aaatcttgac tacagtcagg aaaggaatca

15781 tttctatttc tcctccatgg gagaaaatag ataagagtag aaactgcagg gaaaattatt

15841 tgcataacaa ttcctctact aacaatcagc tccttcctgg agactgccca gctaaagcaa

15901 tatgcattta aatacagtct tccatttgca agggaaaagt ctcttgtaat ccgaatctct

15961 ttttgctttc gaactgctag tcaagtgcgt ccacgagctg tttactaggg atccctcatc

16021 tgtccctccg ggacctggtg ctgcctctac ctgacactcc cttgggctcc ctgtaacctc

16081 ttcagaggcc ctcgctgcca gctctgtatc aggacccaga ggaaggggcc agaggctcgt

16141 tgactggctg tgtgttggga ttgagtctgt gccacgtgtt tgtgctgtgg tgtgtccccc

16201 tctgtccagg cactgagata ccagcgagga ggctccagag ggcactctgc ttgttattag

16261 agattacctc ctgagaaaaa aggttccgct tggagcagag gggctgaata gcagaaggtt

16321 gcacctcccc caaccttaga tgttctaagt ctttccattg gatctcattg gacccttcca

16381 tggtgtgatc gtctgactgg tgttatcacc gtgggctccc tgactgggag ttgatcgcct

16441 ttcccaggtg ctacaccctt ttccagctgg atgagaattt gagtgctctg atccctctac

16501 agagcttccc tgactcattc tgaaggagcc ccattcctgg gaaatattcc ctagaaactt

16561 ccaaatcccc taagcagacc actgataaaa ccatgtagaa aatttgttat tttgcaacct

16621 cgctggactc tcagtctctg agcagtgaat gattcagtgt taaatgtgat gaatactgta

16681 ttttgtattg tttcaattgc atctcccaga taatgtgaaa atggtccagg agaaggccaa

16741 ttcctatacg cagcgtgctt taaaaaataa ataagaaaca actctttgag aaacaacaat

16801 ttctactttg aagtcatacc aatgaaaaaa tgtatatgca cttataattt tcctaataaa

16861 gttctgtact caaatgtagc caccaacagt ttgaaattag tgttactact tggaattttc

16921 tggacgtgct ttttttcccc acaaacccaa aactgagggt tgtgtaatcc tggctacagt

APOA5

AY555191.1 REGION: complement(1..49331)

47521 ggggctagca gtctgacggc ctggatatct gtccccttct ccaggaccct gaaagacagc

47581 cttgagcaag acctcaacaa tatgaacaag ttcctggaaa agctgaggcc tctgagtggg

47641 agcgaggctc ctcggctccc acaggacccg gtgggcatgc ggcggcagct gcaggaggag

47701 ttggaggagg tgaaggctcg cctccagccc tacatggcag aggcgcacga gctggtgggc

47761 tggaatttgg agggcttgcg gcagcaactg aagccctaca cgatggatct gatggagcag

47821 gtggccctgc gcgtgcagga gctgcaggag cagttgcgcg tggtggggga agacaccaag

47881 gcccagttgc tggggggcgt ggacgaggct tgggctttgc tgcagggact gcagagccgc

47941 gtggtgcacc acaccggccg cttcaaagag ctcttccacc catacgccga gagcctggtg

48001 agcggcatcg ggcgccacgt gcaggagctg caccgcagtg tggctccgca cgcccccgcc

48061 agccccgcgc gcctcagtcg ctgcgtgcag gtgctctccc ggaagctcac gctcaaggcc

48121 aaggccctgc acgcacgcat ccagcagaac ctggaccagc tgcgcgaaga gctcagcaga

48181 gcctttgcag gcactgggac tgaggaaggg gccggcccgg acccccagat gctctccgag

48241 gaggtgcgcc agcgacttca ggctttccgc caggacacct acctgcagat agctgccttc

48301 actcgcgcca tcgaccagga gactgaggag gtccagcagc agctggcgcc acctccacca

48361 ggccacagtg ccttcgcccc agagtttcaa caaacagaca gtggcaaggt tctgagcaag

48421 ctgcaggccc gtctggatga cctgtgggaa gacatcactc acagccttca tgaccagggc

48481 cacagccatc tgggggaccc cTGAggatct acctgcccag gcccattccc agctccttgt

48541 ctggggagcc ttggctctga gcctctagca tggttcagtc cttgaaagtg gcctgttggg

48601 tggagggtgg aaggtcctgt gcaggacagg gaggccacca aaggggctgc tgtctcctgc

48661 atatccagcc tcctgcgact ccccaatctg gatgcattac attcaccagg ctttgcaaac

aCatccagcc

48721 ccagcctccc agtgctcatt tgggaatgct catgagttac tccattcaag ggtgagggag

48781 tagggaggga gaggcaccat gcatgtgggt gattatctgc aagcctgttt gccgtgatgc

48841 tggaagcctg tgccactaca tcctggagtt tggctctagt cacttctggc tgcctggtgg

48901 ccactgctac agctggtcca cagagaggag cacttgtctc cccagggctg ccatggcagc

48961 tatcagggga atagaaggga gaaagagaat atcatgggga gaacatgtga tggtgtgtga

49021 atatccctgc tggctctgat gctggtgggt acgaaaggtg tgggctgtga taggagaggg

49081 cagagcccat gtttcctgac atagctctac acctaaataa gggactgaac cctcccaact

49141 gtgggagctc cttaaaccct ctggggagca tactgtgtgc tctccccatc tccagcccct

49201 ccctctgggt tcccaagttg aagcctagac ttctggctca aatgaaatag atgtttatga

49261 tagaagtttg cctggcgtga ctctcatttg gaccatgtct gaaagggtca tagctgaatc

49321 aaactgagta g

NPPC

M64710.1

721 gtgggggcgg ctctgggctt gggagggaca ccccgcgccg gcgggcgcgt ggggctggag

781 catcagagtc ccccgtgctg cagccgcgtg tcccttcacc tgcccgctct ttcctcggac

841 aggtcccgcg aaccccgccg gcagaggagc tggccgagcc gcaggctgcg ggcggcggtc

901 agaagaaggg cgacaaggct cccgggggcg ggggcgccaa tctcaagggc gaccggtcgc

961 gactgctccg ggacctgcgc gtggacacca agtcgcgggc agcgtgggct cgccttctgc

1021 aagagcaccc caacgcgcgc aaatacaaag gagccaacaa gaagggcttg tccaagggct

1081 gcttcggcct caagctggac cgaatcggct ccatgagcgg cctgggatgt TAGtgcggcg

1141 ccccctggcg gcggtgagta cggcccaccc gacgcccagc cccagcccgg cccgggaccg

1201 cccgccgccc agccagcctt cggaggcgcg cgagccgcct ttgctcaagt tgtgctaggc

agccGgcctt

1261 gtttgccagc cgcccccttt attatcccac tttacagaca aagaaagcga aggataacgt

1321 gatcggggaa ctttggcaag gtcagaaacg gctcagcctg gttgaaccca cctggcttct

1381 tctggagaag cagaaacagg cttggtggtg tctcacccac ccctgaaccg tagctgaact

1441 agcagcactg gcccctattg gccagctggt ggggggattg agaggagatc atgggtttgt

1501 gggagcagag aaggaaggtt acacccacaa gtccagggga catcgatcat ctgctggcca

1561 ccatgccccc tgtagtgaga gtagccctct gctggcactg tcagagcgcc cttctgcctg

1621 ggacactccg attcctgtcc cttctctaaa cccaggcagt gggcaaactg gtctgtccag

1681 ggtcctgagg cagctgcag

SEP15

NM_004261.3

601 aaaattggga aggttccctc aagtccaagc ttttgttagg agtgataaac ccaaactgtt

661 cagaggactg caaatcaagt atgtccgtgg ttcagaccct gtattaaagc ttttggacga

721 caatgggaac attgctgaag aactgagcat tctcaaatgg aacacagaca gtgtagaaga

781 attcctgagt gaaaagttgg aacgcataTA Aatcttgctt aaattttgtc ctatcctttt

841 gttaccttat caaatgaaat attacagcac ctagaaaata atttagtttt gcttgcttcc

901 attgatcagt cttttacttg aggcattaaa tatctaatta aatcgtgaaa tggcagtata

961 gtccatgata tctaaggagt tggcaagctt aacaaaaccc attttttata aatgtccatc

1021 ctcctgcatt tgttgatacc actaacaaaa tgctttgtaa cagacttgcg gttaattatg

1081 caaatgatag tttgtgataa ttggtccagt tttacgaaca acagatttct aaattagaga

acagatttTt

1141 ggttaacaag acagatgatt actatgcctc atgtgctgtg tgctctttga aaggaatgac

1201 agcagactac aaagcaaata agatatactg agcctcaaca gattgcctgc tcctcagagt

1261 ctctcctatt tttgtattac ccagctttct ttttaataca aatgttattt atagtttaca

1321 atgaatgcac tgcataaaaa ctttgtagct tcattattgt aaaacatatt caagatccta

1381 cagtaagagt gaaacattca caaagatttg cgttaatgaa gactacacag aaaacctttc

1441 tagggatttg tgtggatcag atacatactt ggcaaatttt tgagttttac attcttacag

1501 aaaagtccat ttaaaagtga tcatttgtaa gaccaaaata taaataaaaa gtttcaaaaa

1561 tctatctgaa tttggaattc ttctggtttg ttctttcatg tttaaaaatg atgtttttca

1621 atgcattttt ttcatgtaag cccttttttt agccaaaatg taaaaatggc tgtaatattt

1681 aaaacttata acatcttatt gttggtaata gtgctttata tttgtctgat tttatttttc

1741 aaagtttttt catttatgaa cacattttca ttggtatatt atttaaggaa tatctcttga

1801 tatagaattt ttatattaaa aatgattttt ctttgcttaa aaaaaaaaaa a

Table S2 Group 2 variants

HBB

NG_000007.3

71761 tgctaatagc agctacaatc cagctaccat tctgctttta ttttatggtt gggataaggc

71821 tggattattc tgagtccaag ctaggccctt ttgctaatca tgttcatacc tcttatcttc

71881 ctcccacagc tcctgggcaa cgtgctggtc tgtgtgctgg cccatcactt tggcaaagaa

71941 ttcaccccac cagtgcaggc tgcctatcag aaagtggtgg ctggtgtggc taatgccctg

72001 gcccacaagt atcacTAAgc tcgctttctt gctgtccaat ttctattaaa ggttcctttg

tcgGtttctt

72061 ttccctaagt ccaactacta aactggggga tattatgaag ggccttgagc atctggattc

72121 tgcctaataa aaaacattta ttttcattgc aatgatgtat ttaaattatt tctgaatatt

72181 ttactaaaaa gggaatgtgg gaggtcagtg catttaaaac ataaagaaat gaagagctag

72241 ttcaaacctt gggaaaatac actatatctt aaactccatg aaagaaggtg aggctgcaaa