Table 2.
List of common sequence variants located within the boundaries of the GAA gene
| Location | Variant | Variant ID | Global allele frequency (GnomAD) | Predictions of pre‐mRNA splicing | CADD score PHRED |
|---|---|---|---|---|---|
| Exon 1A, 5ʹ UTR | c.−338C>G | rs144639114 | 2% | No effect on splicing | 6.524 |
| Exon 1A, 5ʹ UTR | c.−260G>C | rs2304849 | 16% | No effect on splicing | 8.996 |
| Exon 1A, 5ʹ UTR | c.−178G>A | rs77514632 | 2% | No effect on splicing | 9.948 |
| Exon 1B, 5ʹ UTR | c.−75C>G | rs80020206 | 0.9% (3% in African population) | No effect on splicing | 9.989 |
| Intron 1B | c.−33+219G>C | rs4889961 | 75% | No effect on splicing | 0.866 |
| Intron 1B | c.−33+316C>A | rs8077055 | 20% | No effect on splicing | 9.079 |
| Intron 1B | c.−33+317C>T | rs8077056 | 20% | No effect on splicing | 8.579 |
| Intron 1B | c.−33+671A>C | rs55751636 | 31% | No effect on splicing | 1.456 |
| Intron 1B | c.−33+757G>A | rs28413147 | 5% | No effect on splicing | 4.974 |
| Intron 1B | c.−33+903A>C | rs12450199 | 34% | No effect on splicing | 8.196 |
| Intron 1B | c.−33+1104A>G | rs11150841 | 75% | No effect on splicing | 6.976 |
| Intron 1B | c.−33+1172G>A | rs1442315 | 5% | No effect on splicing | 0.064 |
| Intron 1B | c.−33+1190G>T | rs12602593 | 10% | No effect on splicing | 1.784 |
| Intron 1B | c.−33+1309T>C | rs1442314 | 76% | No effect on splicing | 1.752 |
| Intron 1B | c.−32‐1298G>C | rs12602610 | 33% | No effect on splicing | 2.604 |
| Intron 1B | c.−32‐1124C>T | rs58959690 | 20% | No effect on splicing | 5.825 |
| Intron 1B | c.−32‐884T>C | rs145362066 | 0.9% (3% in African population) | No effect on splicing | 3.993 |
| Intron 1B | c.−32‐793C>G | rs55666739 | 2% | No effect on splicing | 4.041 |
| Intron 1B | c.−32‐721G>C | rs75754966 | 2% | Generates a new cryptic splice accepter site | 1.008 |
| Intron 1B | c.−32‐686A>G | rs147264695 | 0.3% (1% in Finnish population) | No effect on splicing | 4.349 |
| Intron 1B | c.−32‐640C>T | rs12600845 | 51% | No effect on splicing | 0.136 |
| Intron 1B | c.−32‐521G>T | rs115060925 | 1% | Generates a new cryptic splice donor site | 0.639 |
| Intron 1B | c.−32‐494C>G | rs140325572 | 2% | No effect on splicing | 0.036 |
| Intron 1B | c.−32‐462G>A | rs74003606 | 5% | No effect on splicing | 0.226 |
| Exon 2 | c.271G>A | rs1800299 | 2% | No effect on splicing | 0.256 |
| Exon 2 | c.324T>C | rs1800300 | 72% | No effect on splicing | 8.391 |
| Exon 2 | c.447G>A | rs2289536 | 0.5% (3% in East Asian population) | No effect on splicing | 1.252 |
| Intron 2 | c.546+293G>A | rs34746710 | 20% | No effect on splicing | 1.899 |
| Intron 2 | c.547‐243C>G | rs8065426 | 67% | No effect on splicing | 2.529 |
| Intron 2 | c.547‐238T>C | rs12452263 | 20% | No effect on splicing | 5.667 |
| Intron 2 | c.547‐67C>G | rs8069491 | 67% | No effect on splicing | 1.337 |
| Intron 2 | c.547‐39T>G | rs12452721 | 67% | Loss of cryptic splice donor site | 2.78 |
| Intron 2 | c.547‐4C>G | rs3816256 | 67% | No effect on splicing | 4.721 |
| Exon 3 | c.596A>G | rs1042393 | 67% | No effect on splicing | 0.548 |
| Exon 3 | c.642C>T | rs1800301 | 18% | No effect on splicing | 1.805 |
| Exon 3 | c.668G>A | rs1042395 | 67% | No effect on splicing | 1.46 |
| Intron 3 | c.692+38C>T | rs2304848 | 3% | Generates a new cryptic splice donor site | 5.574 |
| Intron 3 | c.692+144A>G | rs2304847 | 67% | No effect on splicing | 3.653 |
| Intron 3 | c.692+509T>C | rs8082405 | 66% | No effect on splicing | 3.271 |
| Intron 3 | c.692+674G>C | rs8078350 | 67% | No effect on splicing | 4.501 |
| Intron 3 | c.692+751T>C | rs8068051 | 67% | No effect on splicing | 2.363 |
| Intron 3 | c.693‐586G>A | rs112308142 | 3% | No effect on splicing | 2.71 |
| Intron 3 | c.693‐585T>C | rs8068555 | 67% | No effect on splicing | 4.133 |
| Intron 3 | c.693‐559C>T | rs12602422 | 67% | No effect on splicing | 1.879 |
| Intron 3 | c.693‐491G>A | rs12948631 | 67% | No effect on splicing | 3.629 |
| Intron 3 | c.693‐441C>G | rs12602440 | 67% | Loss of a cryptic splice acceptor site | 7.559 |
| Intron 3 | c.693‐434C>A | rs12941269 | 66% | No effect on splicing | 4.416 |
| Intron 3 | c.693‐414C>G | rs12941289 | 66% | Loss of a cryptic splice acceptor site | 0.077 |
| Intron 3 | c.693‐413A>G | rs12937590 | 67% | Loss of a cryptic splice acceptor site | 1.544 |
| Intron 3 | c.693‐216T>A | rs11150844 | 67% | No effect on splicing | 4.13 |
| Intron 3 | c.693‐94C>T | rs79849256 | 0.2% (3% in East Asian population) | No effect on splicing | 9.666 |
| Intron 3 | c.693‐78C>T | rs74003611 | 6% | No effect on splicing | 0.06 |
| Intron 3 | c.693‐49C>T | rs78855075 | 7% | No effect on splicing | 2.374 |
| Exon 4 | c.852G>A | rs142626724 | 0.6% (1% in European population) | No effect on splicing | 1.095 |
| Intron 4 | c.858+30T>C | rs2304845 | 66% | No effect on splicing | 0.067 |
| Exon 5 | c.921A>T | rs1800303 | 8% | No effect on splicing | 9.101 |
| Intron 5 | c.955+12G>A | rs2252455 | 69% | No effect on splicing | 0.981 |
| Intron 5 | c.955+155C>A | rs9901190 | 5% | No effect on splicing | 7.196 |
| Intron 5 | c.955+167C>T | rs77717164 | 0.7% (6% in East Asian population) | No effect on splicing | 6.348 |
| Intron 5 | c.956‐107G>A | rs2241888 | 73% | No effect on splicing | 5.835 |
| Intron 5 | c.956‐84C>T | rs2241887 | 67% | No effect on splicing | 0.061 |
| Intron 6 | c.1075+13C>T | rs41292402 | 1% | No effect on splicing | 7.496 |
| Exon 8 | c.1203G>A | rs1800304 | 67% | No effect on splicing | 5.972 |
| Exon 8 | c.1286A>G | rs200294882 | 0.07% (1% in East Asian population) | Loss of cryptic splice acceptor site and generates a new cryptic splice donor site | 0.068 |
| Intron 8 | c.1326+132G>A | rs894306 | 67% | No effect on splicing | 1.999 |
| Intron 8 | c.1326+459C>T | rs74679377 | 0.7% (6% in East Asian population) | No effect on splicing | 0.435 |
| Intron 8 | c.1326+460G>A | rs12150323 | 2% | No effect on splicing | 0.322 |
| Intron 8 | c.1327‐514G>A | rs72850826 | 5% | No effect on splicing | 1.914 |
| Intron 8 | c.1327‐356G>T | rs6565640 | 73% | No effect on splicing | 0.258 |
| Intron 8 | c.1327‐321del | rs140385114 | 7% | No effect on splicing | 0.888 |
| Intron 8 | c.1327‐269A>G | rs6565641 | 67% | No effect on splicing | 4.207 |
| Intron 8 | c.1327‐209C>T | rs76604157 | 0.3% (6% in East Asian population) | No effect on splicing | 0.471 |
| Intron 8 | c.1327‐179G>A | rs2278620 | 20% | No effect on splicing | 0.643 |
| Intron 8 | c.1327‐118A>G | rs74003628 | 7% | No effect on splicing | 0.184 |
| Intron 8 | c.1327‐18A>G | rs2278619 | 72% | No effect on splicing | 0.124 |
| Exon 9 | c.1374C>T | rs1800305 | 7% | No effect on splicing | 0.206 |
| Intron 9 | c.1438‐220A>G | rs2278618 | 67% | No effect on splicing | 6.607 |
| Intron 9 | c.1438‐108G>A | rs12944802 | 67% | No effect on splicing | 0.013 |
| Intron 9 | c.1438‐19G>C | rs2304844 | 67% | No effect on splicing | 3.529 |
| Intron 10 | c.1551+42G>A | rs115427918 | 0.9% (3% in African population) | No effect on splicing | 5.792 |
| Intron 10 | c.1551+49C>A | rs2304843 | 67% | No effect on splicing | 7.131 |
| Exon 11 | c.1581G>A | rs1042396 | 23% | No effect on splicing | 6.758 |
| Intron 11 | c.1636+43G>T | rs2304842 | 5% | Generates a new cryptic splice accepter site | 6.859 |
| Intron 11 | c.1636+117del | rs199788201 | 59% | No effect on splicing | 0.045 |
| Intron 11 | c.1636+117C>T | rs12945868 | 11% | No effect on splicing | 0.181 |
| Intron 11 | c.1636+118G>T | rs4889817 | 59% | No effect on splicing | 3.161 |
| Intron 11 | c.1636+205C>T | rs79673008 | 3% | No effect on splicing | 0.013 |
| Intron 11 | c.1636+210G>A | rs79487884 | 5% | No effect on splicing | 1.463 |
| Intron 11 | c.1636+269C>T | rs111625854 | 2% | No effect on splicing | 3.828 |
| Intron 11 | c.1636+284G>C | rs111551014 | 2% | No effect on splicing | 1.81 |
| Intron 11 | c.1636+389C>G | rs7221675 | 63% | No effect on splicing | 0.573 |
| Intron 11 | c.1636+390A>G | rs7209921 | 63% | No effect on splicing | 1.829 |
| Intron 11 | c.1636+404A>G | rs4889818 | 74% | No effect on splicing | 1.902 |
| Intron 11 | c.1637‐185A>G | rs12951255 | 55% | No effect on splicing | 0.576 |
| Exon 12 | c.1726G>A | rs1800307 | 2% | Generates a new cryptic splice acceptor | 0.268 |
| Intron 12 | c.1754+12G>A | rs2304840 | 6% | No effect on splicing | 4.325 |
| Intron 12 | c.1754+100C>T | rs113688685 | 0.9% (3% in African population) | No effect on splicing | 8.142 |
| Intron 12 | c.1754+104C>G | rs2304839 | 5% | No effect on splicing | 0.763 |
| Intron 12 | c.1754+144C>T | rs2304838 | 61% | No effect on splicing | 1.787 |
| Intron 12 | c.1755‐186A>G | rs62075593 | 2% | No effect on splicing | 2.032 |
| Intron 13 | c.1888+21G>A | rs2304837 | 6% | No effect on splicing | 3.378 |
| Intron 14 | c.2040+20A>G | rs2304836 | 72% | No effect on splicing | 2.163 |
| Intron 14 | c.2040+66C>T | rs2304835 | 7% | No effect on splicing | 3.54 |
| Intron 14 | c.2040+69A>G | rs2304834 | 6% | No effect on splicing | 0.027 |
| Intron 14 | c.2041‐64G>A | rs2304833 | 27% | No effect on splicing | 0.371 |
| Exon 15 | c.2065G>A | rs1800309 | 6% | No effect on splicing | 1.783 |
| Exon 15 | c.2133A>G | rs1800310 | 27% | No effect on splicing | 1.134 |
| Intron 15 | c.2189+95C>T | rs72850840 | 5% | No effect on splicing | 3,771 |
| Intron 15 | c.2189+263G>A | rs7221604 | 66% | Generates a new cryptic splice donor site | 0.563 |
| Intron 15 | c.2189+510T>G | rs4889963 | 5% | No effect on splicing | 1.444 |
| Intron 15 | c.2189+607G>A | rs112710614 | 7% | No effect on splicing | 0.189 |
| Intron 15 | c.2189+616T>C | rs139307163 | 5% | No effect on splicing | 1.94 |
| Intron 15 | c.2189+723G>A | rs4889819 | 20% | No effect on splicing | 0.367 |
| Intron 15 | c.2189+729A>G | rs74737410 | 5% | No effect on splicing | 0.498 |
| Intron 15 | c.2189+859A>G | rs4889964 | 5% | No effect on splicing | 1.503 |
| Intron 15 | c.2189+884G>A | rs4889965 | 5% | No effect on splicing | 0.355 |
| Intron 15 | c.2189+1153A>G | rs72850844 | 5% | No effect on splicing | 3.687 |
| Intron 15 | c.2189+1201C>A | rs72850846 | 5% | No effect on splicing | 2.352 |
| Intron 15 | c.2189+1208A>G | rs72850847 | 5% | No effect on splicing | 0.367 |
| Intron 15 | c.2189+1263A>G | rs74700450 | 5% | No effect on splicing | 2.97 |
| Intron 15 | c.2189+1290A>G | rs74003630 | 5% | No effect on splicing | 6.015 |
| Intron 15 | c.2189+1600C>T | rs60668271 | 5% | No effect on splicing | 0.481 |
| Intron 15 | c.2190‐1531G>A | rs74702528 | 0.9% (3% in African population) | No effect on splicing | 0.489 |
| Intron 15 | c.2190‐1463G>A | rs116416508 | 0.9% (3% in African population) | No effect on splicing | 0.328 |
| Intron 15 | c.2190‐1139A>G | rs184803352 | 0.7% (2% in African population | No effect on splicing | 0.095 |
| Intron 15 | c.2190‐1005A>G | rs4889820 | 5% | No effect on splicing | 2.452 |
| Intron 15 | c.2190‐686G>A | rs12452616 | 19% | No effect on splicing | 2.725 |
| Intron 15 | c.2190‐647G>A | rs59362713 | 10% | No effect on splicing | 0.227 |
| Intron 15 | c.2190‐536G>A | rs60429724 | 10% | No effect on splicing | 0.454 |
| Intron 15 | c.2190‐490G>A | rs111477580 | 1% | No effect on splicing | 3.101 |
| Intron 15 | c.2190‐444A>G | rs4889967 | 73% | No effect on splicing | 1.059 |
| Intron 15 | c.2190‐336C>T | rs76178719 | 3% | No effect on splicing | 1.566 |
| Intron 16 | c.2331+20G>A | rs2304832 | 75% | No effect on splicing | 5.346 |
| Intron 16 | c.2331+24T>C | rs2304831 | 15% | No effect on splicing | 0.204 |
| Intron 16 | c.2331+151C>T | rs111537160 | 2% | No effect on splicing | 0.608 |
| Intron 16 | c.2332‐198A>T | rs2304830 | 73% | No effect on splicing | 3.363 |
| Exon 17 | c.2338G>A | rs1126690 | 72% | No effect on splicing | 2.675 |
| Exon 17 | c.2446G>A | rs1800314 | 5% | No effect on splicing | 5.793 |
| Intron 17 | c.2482‐132C>T | rs113824706 | 0.9% (3% in African population) | No effect on splicing | 0.066 |
| Exon 18 | c.2553G>A | rs1042397 | 57% | Weakens a cryptic splice donor site | 1.241 |
| Intron 18 | c.2647‐71G>C | rs4889821 | 5% | No effect on splicing | 3.473 |
| Exon 19 | c.2780C>T | rs1800315 | 2% | No effect on splicing | 0.222 |
| Intron 19 | c.2800‐227C>G | rs9890469 | 66% | No effect on splicing | 0.661 |
| Intron 19 | c.2800‐60G>A | rs55662462 | 0.7% (11% in Latino population) | No effect on splicing | 2.209 |
| Exon 20, 3ʹ UTR | c.*3G>A | rs1800317 | 5% | No effect on splicing | 0.03 |
| Exon 20, 3ʹ UTR | c.*91G>A | rs2229221 | 12% | No effect on splicing | 6.887 |
| Exon 20, 3ʹ UTR | c.*223C>T | rs8132 | 22% | No effect on splicing | 3.025 |
| Exon 20, 3ʹ UTR | c.*419G>T | rs7567 | 19% | No effect on splicing | 4.17 |
Abbreviations: CADD, Combined Annotation‐Dependent Depletion; mRNA, messenger RNA; UTR, untranslated region.