Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PVS1_SupportingPM2BS2
The NM_016816.4(OAS1):c.-1_2delAAT(p.Met1del) variant causes a start lost, conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,828 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
OAS1 (HGNC:8086): (2'-5'-oligoadenylate synthetase 1) This interferon-induced gene encodes a protein that synthesizes 2',5'-oligoadenylates (2-5As). This protein plays a key role in innate cellular antiviral response, and has been implicated in other cellular processes like cell growth and apoptosis. Alternative splicing results in multiple transcript variants with different enzymatic activities. Polymorphisms in this gene have been associated with susceptibility to viral infection, including SARS-CoV-2, and diabetes mellitus, type 1. This gene is located in a cluster of related genes on chromosome 12. [provided by RefSeq, May 2022]
Verdict is Likely_benign. Variant got -1 ACMG points.
PVS1
Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 3 CDS bases. Genomic position: 112907042. Lost 0.002 part of the original CDS.
PM2
Very rare variant in population databases, with high coverage;
Review Status: criteria provided, single submitter
Collection Method: clinical testing
This sequence change affects the initiator methionine of the OAS1 mRNA. The next in-frame methionine is located at codon 2. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with OAS1-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -