Fig. 2. Flowchart of variant filtering steps and results by family.

^*Genetically enriched for IA: severe IA phenotype (multiple, early onset, or ruptured) and common site involvement within families. ACMG = American College of Medical Genetics and Genomics, AD = autosomal dominant, AMP = Association for Molecular Pathology, CADD = Combined Annotation Dependent Depletion, ExAC = exome aggregation consortium, FIA = familial intracranial aneurysm, GERP = Genomic Evolutionary Rate Profiling, GWAS = genome-wide association studies, HI = haploinsufficient, IA = intracranial aneurysm, M-CAP = Mendelian Clinically Applicable Pathogenicity, OMIM = Online Mendelian Inheritance in Man, pLI = the probability of being loss-of-function intolerant, REVEL = rare exome variant ensemble learner, SIFT = Sorting Intolerant From Tolerant