ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.4243-5C>T (rs114402068)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics,PreventionGenetics RCV000242905 SCV000304497 likely benign not specified criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000242905 SCV000331192 benign not specified 2015-08-25 criteria provided, single submitter clinical testing
Invitae RCV001083251 SCV000562318 benign Cystic fibrosis 2020-11-24 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001281936 SCV000603014 likely benign none provided 2019-11-30 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000242905 SCV000697018 likely benign not specified 2019-01-03 criteria provided, single submitter clinical testing Variant summary: The CFTR c.4243-5C>T variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a benign outcome for this variant. 4/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 142/275682 control chromosomes (gnomAD), predominantly observed in the African subpopulation at a frequency of 0.00562 (135/24022). This frequency is slightly lower than the estimated maximal expected allele frequency of a pathogenic CFTR variant (0.0129603), suggesting this is possibly a rare polymorphism found primarily in the populations of African origin. It has been reported in literature in patients with CF and CFTR-related phenotypes without strong evidence for pathogenicity (Zhou_2013, Brennan_2016, Kharrazi_2015, Pagin_2016, Ratkiewicz_2017). In a patient with CFTR-related metabolic syndrome, biallelic pathogenic variants were detected (Prach_2013), supporting for benign outcome. Three ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
Institute for Genomic Medicine (IGM) Clinical Laboratory,Nationwide Children's Hospital RCV000242905 SCV000864326 likely benign not specified 2017-11-14 criteria provided, single submitter clinical testing BP4, BP6; This alteration is predicted to be tolerated by multiple functional prediction tools, and was reported as a benign/likely benign alteration by a reputable source (ClinVar or other correspondence from a clinical testing laboratory).
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000477057 SCV001134145 benign not provided 2019-08-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV001022120 SCV001183817 likely benign Inborn genetic diseases 2018-05-07 criteria provided, single submitter clinical testing General population or sub-population frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance;In silico models in agreement (benign) ;Sub-population frequency in support of benign classification (not ava blue, manual h-w)
Natera, Inc. RCV001083251 SCV001460121 likely benign Cystic fibrosis 2020-04-17 no assertion criteria provided clinical testing

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