The effective implementation of WES and WGS-based diagnostics in the management of children afflicted with genetic diseases and the rapid decrease in the cost of NGS makes the idea of newborn genetic screening very appealing. Such NGS-based screening greatly increases the number of diseases that can be detected compared to conventional newborn screening, as the latter being aimed at early detection of a limited number of inborn diseases. Moreover, genetic testing provides new possibilities for family members of the proband, as many variants responsible for adult-onset conditions are inherited from the parents. However, the idea of NGS-based screening in healthy children raises issues of medical and ethical integrity as well as technical questions including interpretation of the revealed variants. A few pilot studies have shown that both parents and medical professionals have moved forward and are enthused about these new possibilities. However, the number of participants in studies so far has been limited to a few hundreds, which greatly restricts the scope of potential findings. Our current study includes over 7,000 infants born at our center between February 2021 and May 2023. Clinically significant variants that cause treatable or preventable disorders were observed in 0.9% of inconspicuous infants, 2.1% of the screened newborns being found to carry variants associated with monogenic diseases with incomplete penetrance or late onset and 0.3% having chromosomal abnormalities. Here we report our results and address questions regarding interpretation of variants in newborns who were presumed to be healthy.