Methods and processes for non-invasive assessment of genetic variations

A method for determining the presence or absence of a chromosome trisomy, comprising:

• (a) obtaining counts of sequence reads mapped to portions of a reference genome, which sequence reads are reads of circulating cell-free nucleic acid from a test sample from a pregnant female;
• (b) generating a regression for (i) the counts, and (ii) guanine and cytosine (GC) content, for each of the portions of the reference genome for the test sample;
• (c) assessing the goodness of fit of the counts and the GC content to a non-linear regression or a linear regression, thereby generating an assessment;
• (d) normalizing the counts by a process selected according to the assessment, thereby generating normalized counts with reduced GC bias;
• and
• (e) determining the presence or absence of a chromosome trisomy according to the normalized counts.