Submissions for variant NC_000001.11:g.230710700A>G

gnomAD frequency: 0.00110  dbSNP: rs61731497

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000332892	SCV000355406	likely benign	Renal tubular dysgenesis	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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000963786	SCV001110960	likely benign	not provided	2024-01-02	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000963786	SCV005264346	likely benign	not provided		criteria provided, single submitter	not provided
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001357255	SCV001552674	benign	not specified		no assertion criteria provided	clinical testing	The AGT p.Cys51Arg variant was not identified in the literature nor was it identified in LOVD 3.0. The variant was identified in dbSNP (ID: rs61731497) and ClinVar (classified as uncertain significance by Illumina). The variant was identified in control databases in 439 of 282824 chromosomes (2 homozygous) at a frequency of 0.001552 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: European (non-Finnish) in 358 of 129162 chromosomes (freq: 0.002772), Other in 14 of 7222 chromosomes (freq: 0.001939), European (Finnish) in 39 of 25116 chromosomes (freq: 0.001553), Latino in 18 of 35430 chromosomes (freq: 0.000508), African in 9 of 24960 chromosomes (freq: 0.000361) and Ashkenazi Jewish in 1 of 10366 chromosomes (freq: 0.000096), but was not observed in the East Asian or South Asian populations. The p.Cys51 residue is conserved in mammals but not in more distantly related organisms, and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and three of four in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign.
PreventionGenetics, part of Exact Sciences	RCV003930231	SCV004745932	likely benign	AGT-related disorder	2020-06-08	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).