✨SpliceAI

Overview

SpliceAI is an AI annotation model developed by the Illumina Artificial Intelligence Lab to predict splice effects.

The model evaluates probability that a variant disrupts or creates acceptor and donor splice sites. Higher delta scores suggest a stronger predicted effect on RNA splicing.

Splicing defects are a major contributor to human disease, particularly in rare disease and oncology, where many pathogenic variants occur in non-coding regions.

For more details, refer to:

Publication

Jaganathan, et al. Predicting splicing from primary sequence with deep learning. Cell (2019). https://doi.org/10.1016/j.cell.2018.12.015

Professional data source

This data source requires a Professional license. Contact [e-mail] to request access.

Parsing

VCF File

##fileformat=VCFv4.0
##assembly=GRCh37/hg19
##INFO=<ID=SYMBOL,Number=1,Type=String,Description="HGNC gene symbol">
##INFO=<ID=STRAND,Number=1,Type=String,Description="+ or - depending on whether the gene lies in the positive or negative strand">
##INFO=<ID=TYPE,Number=1,Type=String,Description="E or I depending on whether the variant position is exonic or intronic (GENCODE V24lift37 canonical annotation)">
##INFO=<ID=DIST,Number=1,Type=Integer,Description="Distance between the variant position and the closest splice site (GENCODE V24lift37 canonical annotation)">
##INFO=<ID=DS_AG,Number=1,Type=Float,Description="Delta score (acceptor gain)">
##INFO=<ID=DS_AL,Number=1,Type=Float,Description="Delta score (acceptor loss)">
##INFO=<ID=DS_DG,Number=1,Type=Float,Description="Delta score (donor gain)">
##INFO=<ID=DS_DL,Number=1,Type=Float,Description="Delta score (donor loss)">
##INFO=<ID=DP_AG,Number=1,Type=Integer,Description="Delta position (acceptor gain) relative to the variant position">
##INFO=<ID=DP_AL,Number=1,Type=Integer,Description="Delta position (acceptor loss) relative to the variant position">
##INFO=<ID=DP_DG,Number=1,Type=Integer,Description="Delta position (donor gain) relative to the variant position">
##INFO=<ID=DP_DL,Number=1,Type=Integer,Description="Delta position (donor loss) relative to the variant position">
#CHROM	POS	ID	REF	ALT	QUAL	FILTER	INFO
10	92946	.	C	T	.	.	SYMBOL=TUBB8;STRAND=-;TYPE=E;DIST=-53;DS_AG=0.0000;DS_AL=0.0000;DS_DG=0.0000;DS_DL=0.0000;DP_AG=-26;DP_AL=-10;DP_DG=3;DP_DL=35
10	92946	.	C	G	.	.	SYMBOL=TUBB8;STRAND=-;TYPE=E;DIST=-53;DS_AG=0.0008;DS_AL=0.0000;DS_DG=0.0003;DS_DL=0.0000;DP_AG=34;DP_AL=-27;DP_DG=35;DP_DL=1
10	92946	.	C	A	.	.	SYMBOL=TUBB8;STRAND=-;TYPE=E;DIST=-53;DS_AG=0.0004;DS_AL=0.0000;DS_DG=0.0001;DS_DL=0.0000;DP_AG=-10;DP_AL=-48;DP_DG=35;DP_DL=-21
10	92947	.	A	C	.	.	SYMBOL=TUBB8;STRAND=-;TYPE=E;DIST=-54;DS_AG=0.0002;DS_AL=0.0000;DS_DG=0.0000;DS_DL=0.0000;DP_AG=-49;DP_AL=-11;DP_DG=0;DP_DL=34
10	92947	.	A	T	.	.	SYMBOL=TUBB8;STRAND=-;TYPE=E;DIST=-54;DS_AG=0.0002;DS_AL=0.0000;DS_DG=0.0000;DS_DL=0.0000;DP_AG=33;DP_AL=-11;DP_DG=-22;DP_DL=34
10	92947	.	A	G	.	.	SYMBOL=TUBB8;STRAND=-;TYPE=E;DIST=-54;DS_AG=0.0006;DS_AL=0.0000;DS_DG=0.0001;DS_DL=0.0000;DP_AG=33;DP_AL=-11;DP_DG=34;DP_DL=32

Illumina Connected Annotations extracts these INFO fields:

• DS_AG - Δ score (acceptor gain)
• DS_AL - Δ score (acceptor loss)
• DS_DG - Δ score (donor gain)
• DS_DL - Δ score (donor loss)
• DP_AG - Δ position (acceptor gain) relative to the variant position
• DP_AL - Δ position (acceptor loss) relative to the variant position
• DP_DG - Δ position (donor gain) relative to the variant position
• DP_DL - Δ position (donor loss) relative to the variant position

These fields report the predicted splice gain or loss and the relative position of the effect.

Filtering

SpliceAI provides entries across the genome. Many low-scoring entries have limited value, especially in intergenic regions. These entries increase storage requirements and slow annotation.

Illumina Connected Annotations filters out low-confidence entries except within 15 bp of nascent splice sites. In those regions, low-confidence predictions can still help identify potential splice disruption.

JSON output

"spliceAI":[ 
   {
      "hgnc":"BLCAP",
      "acceptorGainDistance":-3,
      "acceptorGainScore":0.3,
      "donorLossDistance":7,
      "donorLossScore":0.9
   },
   { 
      "hgnc":"NNAT",
      "acceptorGainDistance":-1,
      "acceptorGainScore":0.2,
      "donorGainDistance":-2,
      "donorGainScore":0.3
   }
]

Field	Type	Notes
hgnc	string	HGNC gene symbol
acceptorGainDistance	int	± bp from current position
acceptorGainScore	float	range: 0 - 1.0. 1 decimal place
acceptorLossDistance	int	± bp from current position
acceptorLossScore	float	range: 0 - 1.0. 1 decimal place
donorGainDistance	int	± bp from current position
donorGainScore	float	range: 0 - 1.0. 1 decimal place
donorLossDistance	int	± bp from current position
donorLossScore	float	range: 0 - 1.0. 1 decimal place

Interpreting scores

SpliceAI delta scores range from 0 to 1.

The SpliceAI team suggests this interpretation:

Range	Confidence	Pathogenicity
0 ≤ x < 0.1	low	likely benign
0.1 ≤ x ≤ 0.5	medium	likely pathogenic
x > 0.5	high	pathogenic

Resources

• SpliceAI GitHub
• Download URL
• Related paper:

  • Rowlands, et al. Comparison of in silico strategies to prioritize rare genomic variants impacting RNA splicing for the diagnosis of genomic disorders. Scientific Reports (2021). https://doi.org/10.1038/s41598-021-99747-2