Entity reference field pointing to a Configuration Entity
This is no problem, in ui you can configure bundle fields referencing all entity types, content and configuration. And for base fields this is an example from the user entity for a reference field pointing at the configuration entity user_role:

$fields['roles'] = BaseFieldDefinition::create('entity_reference')
  -&gt;setLabel(t('Roles'))
  -&gt;setCardinality(BaseFieldDefinition::CARDINALITY_UNLIMITED)
  -&gt;setDescription(t('The roles the user has.'))
  -&gt;setSetting('target_type', 'user_role');