Submissions for variant NM_000349.3(STAR):c.179-14G>A

gnomAD frequency: 0.00057  dbSNP: rs117578796

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001163637	SCV001325698	uncertain significance	Congenital lipoid adrenal hyperplasia due to STAR deficency	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001354114	SCV004343372	benign	not provided	2024-01-30	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001354114	SCV001548648	uncertain significance	not provided		no assertion criteria provided	clinical testing	The STAR c.179-14G>A variant was not identified in the literature nor was it identified in ClinVar or LOVD 3.0. The variant was identified in dbSNP (ID: rs117578796) and in control databases in 159 of 282294 chromosomes at a frequency of 0.000563 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: East Asian in 155 of 19940 chromosomes (freq: 0.007773), Latino in 2 of 35384 chromosomes (freq: 0.000057), South Asian in 1 of 30550 chromosomes (freq: 0.000033) and European (non-Finnish) in 1 of 128874 chromosomes (freq: 0.000008), but was not observed in the African, Ashkenazi Jewish, European (Finnish) or Other populations. The c.179-14G>A variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. However, 4 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predict a greater than 10% difference in splicing and the creation of a new 3' splice site. However, this information is not predictive enough to assume pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.