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Table 2 Bioinformatics analysis of GFAP collected variants related to Alexander disease

From: Identification of a novel de novo pathogenic variant in GFAP in an Iranian family with Alexander disease by whole-exome sequencing

No.

Position on Chromosome 17

(GRCh37)

HGVS DNA

HGVS protein

Exon/intron

SNP ID

Transcript

Coil

ClinVar

SIFT

MutationTaster

PROVEAN

FATHMM

GERP

ACMG

CADD

PolyPhen-2

1

42987997

c.1157A > G

p.Asn386Ser

E

rs61726471

ENST00000253408

Tail

-

T

DC

N

D

5.13

LP

17.83

B

2

42992647

c.208C > T

p.Arg70Trp

E

rs60343255

ENST00000253408

Head

P

D

DC/P

D

D

4.82

P

24.1

PD

3

42992549

c.306C > A

p.Asn102Lys

E

-

ENST00000586793.1

Coil1A

-

T

DC

N

T/D

4.69

LP

21.8

PD

4

42988006

c.1148C > T

p.Thr383Ile

E

rs267607517

ENST00000586793.1

Tail

P

D

DC/P

D

D

5.13

LP

25.4

PD

5

42992644

c.211G > A

p.Ala71Thr

E

rs267607522

ENST00000586793.1

Head

NP

D

DC/P

N

D

4.82

LP

23.1

PD

6

42984686

c.*29C > T

NA

3UTR

rs370608748

ENST00000588735.1

-

-

-

-

-

-

5.07

B

-

-

7

42988655

c.1076 T > C

p.Leu359Pro

E

rs267607511

ENST00000586793.1

Coil2B

P

D

DC

D

D

4.25

P

30

PD

8

42988652

c.1079A > T

p.Asp360Val

E

rs62636501

ENST00000586793.1

Coil2B

P

D

DC

D

D

4.25

LP

32

PD

9

42988644

c.1087A > G

p.Ile363Val

E

-

ENST00000586793.1

Coil2B

-

D

DC

N

D

4.25

LP

27.3

PD

10

42988641

c.1090G > A

p.Ala364Thr

E

rs58645997

ENST00000586793.1

Coil2B

P

D

DC

D

D

4.25

P

28.8

PD

11

42988631

c.1100G > C

p.Arg367Thr

E

 

ENST00000586793.1

Coil2B

-

D

DC

D

D

4.25

P

28.8

PD

12

42988613

c.1118A > C

p.Glu373Ala

E

rs797044589

ENST00000586793.1

Coil2B

P

D

DC

D

D

4.25

P

31

PD

13

42988612

c.1119G > C

p.Glu373Asp

E

-

ENST00000586793.1

Coil2B

-

D

DC

D

D

4.25

P

25.6

PD

14

42988605

c.1126C > T

p.Arg376Trp

E

rs267607512

ENST00000586793.1

Coil2B

P

D

DC

D

D

4.25

P

29.7

PD

15

42988604

c.1127G > A

p.Arg376Gln

E

-

ENST00000586793.1

Coil2B

-

D

DC

D

D

4.25

P

36

PD

16

42988000

c.1154C > G

p.Ser385Cys

E

rs797044590

ENST00000586793.1

Tail

LP/P

D

DC

D

D

5.13

P

28.2

PD

17

42987997

c.1157A > G

p.Asn386Ser

E

rs61726471

ENST00000586793.1

Tail

-

T

DC

N

D

5.13

LP

17.83

B

18

42987996

c.1158C > A

p.Asn386Lys

E

-

ENST00000586793.1

Tail

-

D

DC

N

D

5.13

LP

24.9

B

19

42985512

c.1177A > C

p.Ser393Arg

E

-

ENST00000253408.5

Tail

-

T

DC

N

-

5.23

LP

22.6

PD

20

42985511

c.1178G > T

p.Ser393Ile

E

rs62635764

ENST00000253408.5

Tail

P

T

DC

N

-

5.23

LP

21.9

B

No.

Position on Chromosome 17

(GRCh37)

HGVS DNA

HGVS protein

Exon/intron

SNP ID

Transcript

Coil

ClinVar

SIFT

MutationTaster

PROVEAN

FATHMM

GERP

ACMG

CADD

PolyPhen-2

21

42985496

c.1193C > A

p.Ser398Tyr

E

rs267607508

ENST00000253408.5

Tail

P

P

DC

N

-

5.23

LP

22.4

PD

22

42985496

c.1193C > T

p.Ser398Phe

E

rs267607508

ENST00000253408.5

Tail

P

D

DC

N

-

5.23

LP

22.7

PD

23

42985454

c.1235C > T

p.Thr412Ile

E

rs1597853099

ENST00000253408.5

Tail

LP

D

DC

D

-

5.13

LP

22.4

PD

24

42985444

c.1245G > A

p.Met415Ile

E

-

ENST00000253408.5

Tail

-

D

P

N

-

5.13

VUS/P

21.8

B

25

42985443

c.1246C > T

p.Arg416Trp

E

rs121909717

ENST00000253408.5

Tail

P

D

DC

D

-

5.13

P

21.2

PD

26

42985439

c.1250A > C

p.Asp417Ala

E

rs267607520

ENST00000253408.5

Tail

P

D

DC

D

-

5.13

LP

22.5

B

27

42984754

c.1260C > T

p.Val420 = 

E

rs779643685

ENST00000253408.5

Tail

-

-

DC

-

-

4.80

LB

18.95

-

28

42984737

c.1277A > T

p.Gln426Leu

E

rs267607521

ENST00000253408.5

Tail

P

D

DC

D

-

5.34

LP

18.64

PD

29

42987511

c.1289G > A

p.Arg430His

E

rs748860341

ENST00000435360.2

Tail

LP

D

DC/P

D

D

4.78

LP

15.13

PD

30

42987510

c.1290C > A

p.Arg430 = 

E

rs775524073

ENST00000435360.2

Tail

LP

D

P

-

-

4.78

VUS/P

11.06

-

31

42992668

c.187A > C

p.Lys63Gln

E

rs60095124

ENST00000586793.1

Head

P

D

DC/P

N

D

4.82

LP

23.5

B

32

42992658

c.197G > A

p.Arg66Gln

E

rs797044569

ENST00000586793.1

Head

Conflict

D

DC

D

D

5.89

LP

29

PD

33

42992647

c.208C > T

p.Arg70Trp

E

rs60343255

ENST00000586793.1

Head

P

D

DC/P

D

D

4.82

P

24.1

PD

34

42992646

c.209G > A

p.Arg70Gln

E

rs267607510

ENST00000586793.1

Head

VUS

D

DC/P

N

D

4.82

P

22.2

PD

35

42992641

c.214G > A

p.Glu72Lys

E

rs267607523

ENST00000586793.1

Head

P

D

DC

D

D

4.82

P

24

B

36

42992636

c.219G > C

p.Met73Ile

E

-

ENST00000586793.1

Coil1A

-

D

DC

N

D

4.82

P

23

B

37

42992636

c.219G > T

p.Met73Ile

E

-

ENST00000586793.1

Coil1A

-

D

DC

N

D

4.82

P

23

B

38

42992634

c.221 T > C

p.Met74Thr

E

rs267607504

ENST00000586793.1

Coil1A

P

D

DC

N

D

4.82

P

22.3

B

39

42992629

c.226C > T

p.Leu76Phe

E

rs57120761

ENST00000586793.1

Coil1A

P

D

DC

D

D

4.82

P

26.7

PD

40

42992624

c.231 T > A

p.Asn77Lys

E

-

ENST00000586793.1

Coil1A

-

D

DC

D

D

4.82

P

23.3

PD

No.

Position on Chromosome 17

(GRCh37)

HGVS DNA

HGVS protein

Exon/intron

SNP ID

Transcript

Coil

ClinVar

SIFT

MutationTaster

PROVEAN

FATHMM

GERP

ACMG

CADD

PolyPhen-2

41

42992623

c.232G > A

p.Asp78Asn

E

rs797044571

ENST00000586793.1

Coil1A

P

D

DC

D

D

4.82

P

26

PD

42

42992623

c.232G > C

p.Asp78His

E

-

ENST00000591880.1

Coil1A

-

D

DC

D

-

3.39

VUS/P

26

PD

43

42992621

c.234C > G

p.Asp78Glu

E

-

ENST00000586793.1

Coil1A

-

D

DC

D

D

4.82

P

26

PD

44

42992620

c.235C > T

p.Arg79Cys

E

rs59793293

ENST00000586793.1

Coil1A

P

D

DC

D

D

4.82

P

24.9

PD

45

42992619

c.236G > A

p.Arg79His

E

rs59285727

ENST00000586793.1

Coil1A

P

D

DC

D

D

4.82

P

24.6

PD

46

42992619

c.236G > C

p.Arg79Pro

E

rs59285727

ENST00000586793.1

Coil1A

P

D

DC

D

D

4.82

P

26.8

PD

47

42992619

c.236G > T

p.Arg79Leu

E

rs59285727

ENST00000586793.1

Coil1A

P

D

DC

D

D

4.82

P

26.7

B

48

42992605

c.250A > T

p.Ile84Phe

E

-

ENST00000587997.1

Coil1A

-

D

DC

D

D

5.07

LP

24.3

B

49

42992596

c.256_259delinsGAGT

p.Lys86_Val87delinsGluPhe

E

rs267607501

ENST00000586793.1

Coil1A

P

-

-

-

-

 

LP

-

-

50

42992596

c.259G > A

p.Val87Ile

E

rs267607518

ENST00000586793.1

Coil1A

P

D

DC

N

D

4.69

P

24

PD

51

42992593

c.262C > T

p.Arg88Cys

E

rs61622935

ENST00000586793.1

Coil1A

P

D

DC

D

D

4.69

P

28.2

PD

52

42992593

c.262C > A

p.Arg88Ser

E

rs61622935

ENST00000586793.1

Coil1A

P

D

DC

D

D

4.69

P

31

PD

53

42992577

c.278A > C

p.Gln93Pro

E

rs797044574

ENST00000586793.1

Coil1A

P

D

DC

D

D/T

4.69

LP

27.2

PD

54

42992553

c.302 T > C

p.Leu101Pro

E

rs267607516

ENST00000586793.1

Coil1A

P

D

DC

D

D

4.69

LP

24.3

PD

55

42992482

c.365_373dup

p.Arg124_Leu125insGlnLeuArg

E

rs797044575

ENST00000586793.1

Coil1B

P

−

−

−

−

−

LP

−

−

56

42992487

c.368 T > C

p.Leu123Pro

E

−

ENST00000586793.1

Coil1B

−

D

DC

D

D

4.69

LP

24.2

PD

57

42992470

c.380_385dupGCGGCT

p.Leu127_Asp128dup

E

−

ENST00000586793.1

Coil1B

 

−

−

−

−

−

LP

−

−

58

42992473

c.382G > A

p.Asp128Asn

E

rs267607509

ENST00000586793.1

Coil1B

P

D

DC

D

D/T

4.57

LP

24.2

PD

59

42991449

c.469G > A

p.Asp157Asn

E

rs59291670

ENST00000586793.1

Coil1B

B

D

DC

N

D/T

5.55

B

24.5

B

60

42992802

c.53G > T

p.Gly18Val

E

−

ENST00000586793.1

Head

 

T

P

N

D

3.25

VUS/P

1.67

B

No.

Position on Chromosome 17

(GRCh37)

HGVS DNA

HGVS protein

Exon/intron

SNP ID

Transcript

Coil

ClinVar

SIFT

MutationTaster

PROVEAN

FATHMM

GERP

ACMG

CADD

PolyPhen-2

61

42991103

c.611A > G

p.His204Arg

E

−

ENST00000586793.1

Coil1B

−

D

DC

D

D

4.71

LP

25

PD

62

42991101

c.613G > A

p.Glu205Lys

E

rs267607507

ENST00000586793.1

Coil1B

P

D

DC

D

D

4.71

LP

25.1

PD

63

42991097

c.617A > C

p.Glu206Ala

E

-

ENST00000586793.1

Coil1B

−

D

DC

D

D

4.71

P

33

PD

64

42990798

c.619G > A

p.Glu207Lys

E

rs267607500

ENST00000586793.1

Coil1B

P

D

DC

D

D

4.8

P

34

PD

65

42990798

c.619G > C

p.Glu207Gln

E

rs267607500

ENST00000586793.1

Coil1B

P

D

DC

D

D

4.8

P

33

PD

66

42990797

c.620A > T

p.Glu207Val

E

rs1555574517

ENST00000586793.1

Coil1B

LP

D

DC

D

D

4.8

P

32

PD

67

42990789

c.628G > A

p.Glu210Lys

E

rs57661783

ENST00000586793.1

Coil1B

P

D

DC

D

D

4.92

LP

31

PD

68

42990725

c.692 T > A

p.Leu231His

E

rs797044577

ENST00000586793.1

Coil2A

P

D

DC

D

D

4.92

LP

24.9

PD

69

42990713

c.704 T > C

p.Leu235Pro

E

rs60269890

ENST00000586793.1

Coil2A

P

D

DC

D

D

4.92

LP

24.9

PD

70

42990702

c.715C > G

p.Arg239Gly

E

rs58064122

ENST00000586793.1

Coil2A

VUS

D

DC

D

D

4.92

LP

25.3

PD

71

42990702

c.715C > T

p.Arg239Cys

E

rs58064122

ENST00000586793.1

Coil2A

P

D

DC

D

D

4.92

LP

25.3

PD

72

42990701

c.716G > A

p.Arg239His

E

rs59565950

ENST00000586793.1

Coil2A

P

D

DC

D

D

4.92

P

23.9

PD

73

42990693

c.724 T > A

p.Tyr242Asn

E

−

ENST00000586793.1

Coil2A

−

D

DC

D

D

4.92

LP

25

PD

74

42990686

c.731C > T

p.Ala244Val

E

rs61497286|

ENST00000586793.1

Coil2A

P

D

DC

N

D

4.94

LP

24.3

PD

75

42990678

c.739 T > C

p.Ser247Pro

E

rs267607519

ENST00000586793.1

Coil2A

P

D

DC/P

D

D

5.07

LP

23.1

PD

76

42990647

c.770A > G

p.Tyr257Cys

E

rs26760750

ENST00000586793.1

Coil2B

P

D

DC

D

D

5.07

LP

25.5

PD

77

42990639

c.778A > C

p.Lys260Gln

E

−

ENST00000586793.1

Coil2B

-

D

DC

D

D

5.07

LP

28.9

PD

78

42989147

c.799G > C

p.Ala267Pro

E

rs797044581

ENST00000586793.1

Coil2B

P

D

DC

D

D

4.42

LP

27.1

PD

79

42989143

c.803C > A

p.Ala268Asp

E

rs797044582

ENST00000586793.1

Coil2B

P

D

DC

D

D

4.42

LP

25.7

PD

80

42989137

c.809G > C

p.Arg270Pro

E

−

ENST00000586793.1

Coil2B

−

D

DC

D

D

4.42

LP

25.2

PD

No.

Position on Chromosome 17

(GRCh37)

HGVS DNA

HGVS protein

Exon/intron

SNP ID

Transcript

Coil

ClinVar

SIFT

MutationTaster

PROVEAN

FATHMM

GERP

ACMG

CADD

PolyPhen-2

81

42989119

c.827G > T

p.Arg276Leu

E

rs121909719

ENST00000586793.1

Coil2B

P

D

DC

D

D

4.42

LP

29.8

PD

82

42989078

c.868C > G

p.Gln290Glu

E

rs797044583

ENST00000586793.1

Coil2B

P

D

DC

D

D

4.38

LP

24.6

PD

83

42988797

c.934G > T

p.Glu312Ter

 

rs763868966

ENST00000586793.1

Coil2B

VUS

−

DC

−

−

4.65

P

22.8

−

84

42988743

c.988C > G

p.Arg330Gly

E

rs267607513

ENST00000586793.1

Coil2B

P

D

DC

D

D

4.51

LP

41

PD

85

42988737

c.994G > A

p.Glu332Lys

E

rs267607514

ENST00000586793.1

Coil2B

P

D

DC

D

D

4.51

LP

23.1

PD

86

42985511

c.1178G > T

p.Ser393Ile

E

rs62635764

ENST00000253408.5

Coil2B

P

T

DC

N

−

5.23

LP

24

B

87

42992483

c.372_373insGAA

p.Arg124_Leu125insGlu

E

-

ENST00000586793.1

Coil1B

-

-

-

−

−

4.63

LP

15.82

−

88

42990689

c.726_728dupAGG

p.E243dup

E

-

ENST00000586793.1

Coil1B

-

-

-

−

−

4.92

LP

16.67

−

89

42990716

c.701C > A

p.Ala234Asp

E

rs1353739896

ENST00000592320.1

Coil2A

-

T

DC/P

D

D

4.25

LP

19.72

PD

90

42990801

c.619-3C > G

NA

I

rs112611995

ENST00000586793.1

-

P

-

-

-

-

-

VUS/P

-

-

91

42992582

c.273A > C

p.Glu91Asp

E

-

ENST00000586793.1

Coil1A

-

D

DC

D

D

4.69

LP

25.6

PD

92

42992581

c.274C > G

p.Gln92Glu

E

-

ENST00000586793.1

Coil1A

-

D

DC

N

D

4.69

LP

24.9

PD

93

42992476

c.378_379dup

p.Leu127ArgfsTer26

E

-

ENST00000586793.1

Coil1B

-

-

-

-

-

4.58

P

17.26

-

94

42988612

c.1119G > C

p.Glu373Asp

E

-

ENST00000435360.2

Coil2B

-

D

DC

D

D

4.25

P

21.9

PD

95

42989044

c.902G > A

p.Gly301Asp

E

-

ENST00000586793.1

Coil2B

-

D

DC

D

D

4.38

LP

25.3

PD

96

42990644

c.773G > C

p.Arg258Pro

E

rs61726468

ENST00000586793.1

Coil2B

P

D

DC

D

D

5.07

LP

26

PD

97

42989155

c.791 T > C

p.Leu264Pro

E

rs797044579

ENST00000586793.1

Coil2B

P

D

DC

D

D

4.42

LP

25.3

PD

98

42992579

c.276G > T

p.Gln92His

E

-

ENST00000586793.1

Coil1A

-

D

DC

D

D

4.69

LP

24.5

PD

  1. All the variants were analyzed based on the NM_002055, D damaging, T tolerated, DC disease causing, B benign, P polymorphism, LP likely pathogenic, P pathogenic, PD probably damaging, VUS variant of unknown significance, N neutral