Override a template for only one route I want override the region default template. I did that with a hook theme from my module. 
I want override the region custom template but only for the front page. How can I do that?
You need to implement hook_theme_suggestions_HOOK_alter() in your theme.
For siderbar_first region it would look like follows:

/**
 * Implements hook_theme_suggestions_HOOK_alter().
 */
function THEMENAME_theme_suggestions_region_alter(&amp;$suggestions, $vars) {
  if ($vars['elements']['#region'] == 'sidebar_first' &amp;&amp; Drupal::service('path.matcher')-&gt;isFrontPage()) {
    $suggestions[] = 'region__sidebar_first__front';
  }
}


Now region--sidebar-first--front.html.twig can be used for theming sidebar on the front page.