Table 1 Overview of functionally validated splice variants

From: ABCA4-associated disease as a model for missing heritability in autosomal recessive disorders: novel noncoding splice, cis-regulatory, structural, and recurrent hypomorphic variants

c.notation

g.notation (hg19/chr1)

Intron

Effect on splicing

r.notation

p.notation

Size PE/ skipped exon

c.position PE start

c.position PE stop

Recurrence and AF in our cohort (n = 67)

Recurrence in Dutch cohort (n = 36)

GoNL frequency (n = 499)

1000 Genomes EUR frequency (n = 669)

gnomAD NFE frequency (n = 7498)

Functional assays

c.161–23T>G

g.94577158A>C

2

Exon 3 skip

r.[=, 161_302del]

p.[=, Cys54Serfs*14]

142

161

302

1 (0.7%)

0 (0%)

/

/

/

This study

c.769–784C>T

g.94549781G>A

6

Inclusion PE

r.[=, 768_769ins769-617_769-778]

p.[=, Leu257Aspfs*3]

162

769–778

769–617

1 (0.7%)

7 (9.7%)

0.8%

0.7%

0.4%

Sangermano et al. this issue

c.859–540C>G

g.94546814G>C

7

Inclusion PE

r.858_859ins859-545_859-685;

p.(Phe287Tyrfs*33)

141

859–685

859–545

1 (0.7%)

0 (0%)

/

/

 

This study

c.3191–11T>A

g.94508465A>T

21

Inclusion 9 bp

r.3190_3191ins3191-1_3191-9,

p.(Gly1064delins ValProProGly)

9

3191–9

3191–1

1 (0.7%)

0 (0%)

/

/

/

This study

c.4253+43G>A

g.94496509C>T

28

Exon 28 skip

r.[=, 4129_4253del]

p.[=,Ile1377Hisfs*3]

125

4129

4253

8 (6%)

9 (12.5%)

0.5%

0.1%

0.5%

Sangermano et al. this issue

c.4539+1106C>T

g.94493895G>A

30

Inclusion PE

r.[4539_4540ins4539+1033_4539+1100; r.4539_4540ins4539+989_4539+1100]

p.[Arg1514Glyfs*3; p.Arg1514Valfs*31]

68; 112

4539+1033; 4539+989

4539+1100; 4539+1100

2 (1.5%)

0 (0%)

/

/

/

This study; Sangermano et al. this issue

c.4539+2001G>A

g.94493000C>T

30

Inclusion PE

r.[=, 4539_4540ins4539+1891_4540-2162]

p.[=, Arg1514Leufs*36]

345

4539+1891

4540–2162

7 (5.2%)

1 (1.4%)

/

/

0.000666578%

Albert et al. 2018

c.4539+2064C>T

g.94492937G>A

30

Inclusion PE

r.[=, 4539_4540ins4539+1891_4540-2162]

p.[=, Arg1514Leufs*36]

345

4539+1891

4540–2162

2 (1.5%)

0 (0%)

/

/

/

This study

c.5197–557G>T

g.94481967C>A

36

Inclusion PE

r.5196_5197ins5197-563_5197-750

p.(Met1733*)

188

5197–750

5197–563

1 (0.7%)

0 (0%)

/

/

/

This study

  1. Different notations, effect on splicing, recurrence in the selected cohort of this study and of a Dutch cohort (Sangermano et al. this issue), both mainly composed of monoallelic patients are represented.26,38 AF allele frequency, GoNL Genome of the Netherlands database, gnomAD NFE the Genome Aggregation Database (gnomAD) non-Finnish European population, PE pseudo-exon, 1000 Genomes EUR 1000 Genomes European population.
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