Submissions for variant NM_000204.5(CFI):c.905-3T>C

gnomAD frequency: 0.00014  dbSNP: rs377535161

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000279140	SCV000446879	uncertain significance	Atypical hemolytic-uremic syndrome with I factor anomaly	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.
Blueprint Genetics	RCV000788266	SCV000927318	uncertain significance	not provided	2017-06-27	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV001821055	SCV002065029	uncertain significance	not specified	2017-09-14	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000788266	SCV002275953	uncertain significance	not provided	2023-12-03	criteria provided, single submitter	clinical testing	This sequence change falls in intron 7 of the CFI gene. It does not directly change the encoded amino acid sequence of the CFI protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs377535161, gnomAD 0.08%). This variant has not been reported in the literature in individuals affected with CFI-related conditions. ClinVar contains an entry for this variant (Variation ID: 347164). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002294309	SCV002587693	likely benign	Atypical hemolytic-uremic syndrome	2020-02-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004609367	SCV005107459	uncertain significance	Inborn genetic diseases	2024-04-11	criteria provided, single submitter	clinical testing	The c.905-3T>C intronic alteration consists of a T to C substitution 3 nucleotides before coding exon 8 in the CFI gene. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000788266	SCV002034143	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000788266	SCV002037364	likely benign	not provided		no assertion criteria provided	clinical testing