ClinVar Miner

Submissions for variant NM_000492.4(CFTR):c.1584G>A (p.Glu528=)

gnomAD frequency: 0.01670  dbSNP: rs1800095
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Total submissions: 23
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000036518 SCV000110847 benign not specified 2014-10-17 criteria provided, single submitter clinical testing
Invitae RCV000231696 SCV000284997 benign Cystic fibrosis 2024-02-01 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV001027903 SCV000466516 likely benign CFTR-related disorder 2018-03-06 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.
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics RCV000422767 SCV000511145 likely benign not provided 2016-09-21 criteria provided, single submitter clinical testing Converted during submission to Likely benign.
GeneDx RCV000036518 SCV000512574 likely benign not specified 2017-12-26 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000422767 SCV000602998 likely benign not provided 2023-11-27 criteria provided, single submitter clinical testing
Johns Hopkins Genomics, Johns Hopkins University RCV000231696 SCV000886894 likely benign Cystic fibrosis 2019-08-06 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000422767 SCV000889291 likely benign not provided 2022-12-19 criteria provided, single submitter clinical testing
CFTR-France RCV000231696 SCV001169175 benign Cystic fibrosis 2018-01-29 criteria provided, single submitter curation the variant does not result in CFTR-RD neither
Ambry Genetics RCV000231696 SCV001172721 benign Cystic fibrosis 2017-04-17 criteria provided, single submitter clinical testing This alteration is classified as 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.
CeGaT Center for Human Genetics Tuebingen RCV000422767 SCV001334750 benign not provided 2024-01-01 criteria provided, single submitter clinical testing CFTR: BP4, BS1, BS2
Genome-Nilou Lab RCV000231696 SCV001737309 likely benign Cystic fibrosis 2021-06-10 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001588847 SCV001822063 uncertain significance Congenital bilateral aplasia of vas deferens from CFTR mutation 2021-07-22 criteria provided, single submitter clinical testing
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center RCV000422767 SCV002499183 uncertain significance not provided 2022-01-18 criteria provided, single submitter clinical testing BS2, PS3_supporting, PM3
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV000231696 SCV002507360 uncertain significance Cystic fibrosis 2020-07-23 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000119037 SCV002529681 benign Hereditary pancreatitis 2020-09-01 criteria provided, single submitter curation
Institute of Human Genetics, University of Leipzig Medical Center RCV000231696 SCV002573929 uncertain significance Cystic fibrosis 2022-09-05 criteria provided, single submitter curation This variant was identified in 2 unrelated patients with a clinically confirmed diagnosis of cystic fibrosis. The variant was classified in the context of a project re-classifying variants in the German Cystic Fibrosis Registry (Muko.e.V.). Link: https://www.muko.info/angebote/qualitaetsmanagement/register/cf-einrichtungen/mukoweb. Criteria applied: PS3_SUP, BS1, BS2, BP7
PreventionGenetics, part of Exact Sciences RCV001027903 SCV004793380 benign CFTR-related disorder 2019-04-01 criteria provided, single submitter clinical testing This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000036518 SCV000060173 not provided not specified 2013-09-27 no assertion provided clinical testing Glu528Glu in exon 11 of CFTR (c.1584G>A, historically known as c.1716G>A): This variant has been shown to result in exon skipping in about 10% of transcripts; however, it is prevalent in many populations (highest allele frequency 6.3% in Puerto Ricans; 1000 Genomes Project; rs1800095) and therefore not expected to cause highly penetrant, Mendelian disease. Consistent with this, it has been identified in combination with a severe CF-causing variant in control populations (Rosendahl 2013). However, several studies have suggested that it may be a predisposing factor to idiopathic chronic pancreatitis, although it is unclear if this predisposition is statistically significant (Casals 2004; Rosendahl 2013; Maire 2003). In summary, this variant may be a risk factor for CF-related disease (chronic pancreatitis). It is not expected to lead to disease on its own or in combination with a pathogenic CFTR variant, but may act in conjunction with other genetic and/or environmental risk factors.
GeneReviews RCV000119037 SCV000153743 not provided Hereditary pancreatitis no assertion provided literature only
GenomeConnect, ClinGen RCV000844954 SCV000986779 not provided Pancreatitis no assertion provided phenotyping only Variant interpretted as Uncertain significance and reported on 02/20/2018 by GTR ID 500068. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Natera, Inc. RCV001027903 SCV001190626 likely benign CFTR-related disorder 2019-05-20 no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV001027903 SCV002507444 uncertain significance CFTR-related disorder 2020-07-23 no assertion criteria provided clinical testing

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