It is widely acknowledged that the RefSeq and Ensembl annotations differ significantly due to differences in methodology and information resources. Generally, RefSeq annotation prioritizes experimental evidence, while Ensembl annotation incorporates more computational predictions and includes more novel splicing variants. The choice of an annotation depends on the specific need; for example, RefSeq is commonly used for variant studies , while Ensembl annotations are preferred for extensive research initiatives such as ENCODE, gnomAD , and GTEx. Reference: Zhang, Q., and Shao, M. (2023). Transcript assembly and annotations: Bias and adjustment. PLoS Comput Biol 19, e1011734. 10.1371/journal.pcbi.1011734.