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✅ Severe acute respiratory syndrome coronavirus-2 (SARS‑CoV‑2) is a strain of coronavirus that causes COVID-19 that was first identified in Wuhan of, China, on 2019 (Coronaviridae Study Group of the International Committee on Taxonomy of Viruses, 2020). Omicron variant is one of the SARS-CoV-2 variants that was first informed to WHO (World Health Organization) via South Africa (Network for Genomics Surveillance) on 24 November 2021 (Quarleri et al., 2020). The omicron was first detected in Botswana, and then the variant has spread to become omicron's predominant variant in circulation worldwide (Gowrisankar et al., 2022). Behind the original BA.1 variant (the first dominant omicron variant), several subvariants of omicron, such as BA.2, BA.3, BA.4, and BA.5 (Yao et al., 2022). Omicron subvariants BA.4 and BA.5 were classified as V-22APR-03 and V-22APR-04 by the VTG. BA.4 was designated based on potentially biologically significant mutations in spike. The BA.4 mutations are NSP4: L438 (WT, wild type); S: 69/70 deletion, L452R, F486V, Q493 (WT); ORF 7b: L11F; N: P151S and the S gene 69/70 deletion. The BA.5 has similar mutations/deletions with BA.4 except M: D3N; ORF 6: D61 (WT); ORF 7b: L11 (WT); N: P151 (WT); synonymous SNPs: A27038G, and C27889T (UK health security agency, 2022). Some people believe that the currently used vaccines are ineffective against new subvariants (Ba.4 and BA.5), which is why they do not get vaccinated. This study aimed to investigate the Ba.4 and BA.5 mutations by Bioinformatic analysis.