Submissions for variant NM_001081.4(CUBN):c.5926+5G>A

gnomAD frequency: 0.00019  dbSNP: rs143301088

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000367668	SCV000361690	likely benign	Imerslund-Grasbeck syndrome type 1	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	RCV001495663	SCV001700347	likely benign	Imerslund-Grasbeck syndrome	2025-01-13	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV003736697	SCV004564023	uncertain significance	not provided	2023-10-14	criteria provided, single submitter	clinical testing	The CUBN c.5926+5G>A variant (rs143301088), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 299449). This variant is found in the Admixed American population with an allele frequency of 0.4% (136/5,372 alleles) in the Genome Aggregation Database. This is an intronic variant in a highly conserved nucleotide, and computational analyses (Alamut v.2.11) predict that this variant may impact splicing by weakening the nearby canonical donor splice site. Due to limited information, the clinical significance of the c.5926+5G>A variant is uncertain at this time.
Mayo Clinic Laboratories, Mayo Clinic	RCV003736697	SCV005410950	uncertain significance	not provided	2024-08-15	criteria provided, single submitter	clinical testing	BS1, PP3
PreventionGenetics, part of Exact Sciences	RCV003920230	SCV004728238	likely benign	CUBN-related disorder	2019-05-27	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).