Methods and processes for non-invasive assessment of genetic variations

A computer-implemented method for determining fetal fraction based on a copy number variation in a maternal genome, comprising:

• (a) sequencing a test sample from a pregnant female bearing a fetus by a non-targeted massively parallel sequencing process that generates nucleotide sequence reads, the test sample comprising circulating cell-free nucleic acid from (i) a maternal genome and (ii) a fetal genome;
• mapping the sequence reads to genomic sections of a reference genome;
• and counting the sequence reads mapped to the genomic sections of the reference genome, thereby obtaining counts of sequence reads mapped to the genomic sections of the reference genome;
• (b) normalizing, using a microprocessor, the counts mapped to the genomic sections of the reference genome, thereby providing normalized counts for the genomic sections;
• (c) identifying a first elevation of the normalized counts for a first set of genomic sections significantly different than a second elevation of the normalized counts for a second set of genomic sections, wherein the first set of genomic sections and the second set of genomic sections are within the same chromosome;
• (d) determining a copy number variation in the maternal genome for the first set of genomic sections based on the identified first and second elevations;
• (e) determining a categorization for the copy number variation in the maternal genome by comparing the first elevation to expected elevations for predetermined copy number variation categorizations;
• and
• (f) determining, using a microprocessor, a fetal fraction of the circulating cell-free nucleic acid according to the first elevation and a deviation from an expected elevation of normalized counts for the categorization.