Submissions for variant NM_144997.7(FLCN):c.396+4A>G

gnomAD frequency: 0.00020  dbSNP: rs370353839

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000463405	SCV000549461	likely benign	Birt-Hogg-Dube syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000570650	SCV000673403	likely benign	Hereditary cancer-predisposing syndrome	2019-03-05	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
GeneDx	RCV001570953	SCV001795330	uncertain significance	not provided	2019-12-31	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; In-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.
Sema4, Sema4	RCV000570650	SCV002530136	uncertain significance	Hereditary cancer-predisposing syndrome	2021-09-29	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV002268081	SCV002551370	uncertain significance	not specified	2023-08-15	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003418189	SCV004115712	uncertain significance	FLCN-related disorder	2023-10-09	criteria provided, single submitter	clinical testing	The FLCN c.396+4A>G variant is predicted to interfere with splicing. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.037% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/17-17129486-T-C). It has conflicting interpretations of likely benign and uncertain significance in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/409395/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001570953	SCV001809246	uncertain significance	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001570953	SCV001929509	uncertain significance	not provided		no assertion criteria provided	clinical testing