ClinVar Miner

Submissions for variant NM_000492.4(CFTR):c.-4G>C (rs369326781)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001089310 SCV000074202 likely benign Cystic fibrosis 2020-11-13 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000173140 SCV000224229 likely benign not specified 2015-05-18 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000173140 SCV000697030 likely benign not specified 2019-02-04 criteria provided, single submitter clinical testing Variant summary: The variant, CFTR c.-4G>C is located in the untranslated mRNA region upstream of the initiation codon. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 7.6e-05 in 277043 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in CFTR causing Cystic Fibrosis (7.6e-05 vs 0.013), allowing no conclusion about variant significance. The variant was identified in CF patients, who had F508del on the other chromosome (Zielenski, 1991). Sick kids database references the variant as it is found in strong association with R117H. The variant was reportedly identified in cis with T5, R117H and R117H-T5 complex allele (Hadd, 2004; Lucarelli, 2010; Regan, 2015, respectively). Lastly, the variant of interest has been referred as polymorphism in published reports (Miller, 1996). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000588606 SCV000885196 benign none provided 2019-11-13 criteria provided, single submitter clinical testing
Ambry Genetics RCV001023400 SCV001185269 likely benign Inborn genetic diseases 2018-08-23 criteria provided, single submitter clinical testing Seen in conjunction with two deleterious mutations confirmed in trans in symptomatic individuals
Johns Hopkins Genomics, Johns Hopkins University RCV001089310 SCV001425334 likely benign Cystic fibrosis 2019-12-14 criteria provided, single submitter clinical testing
Natera, Inc. RCV001089310 SCV001465599 likely benign Cystic fibrosis 2020-04-23 no assertion criteria provided clinical testing

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