The RNF213 genetic variant could lead to vascular fragility (including medial thinness), which may make vessels more vulnerable to hemodynamic stress and secondary insults, and these genetic variant also facilitate the development of the formation of basal collaterals in the setting of large intracranial arterial stenosis, including ICAS.[32]. The gene discussed is RNF213; the disease is familial isolated congenital asplenia.