If I CMD+R on Hacker News, it reloads the page. If I do it on outlook.office.com, it starts drafting a reply to the email I have selected. Reload button does the same thing everywhere.
This is one thing I'm grateful for as a Firefox user, I can disallow websites from overriding built-in shortcuts both globally or on a site-by-site basis. I don't believe Safari offers this unfortunately.