ClinVar Miner

Submissions for variant NM_033028.5(BBS4):c.137A>G (p.Lys46Arg) (rs75295839)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000177393 SCV000229244 benign not specified 2015-02-12 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000177393 SCV000315044 benign not specified criteria provided, single submitter clinical testing
GeneDx RCV000425800 SCV000329107 uncertain significance not provided 2016-04-08 criteria provided, single submitter clinical testing The K46R variant in the BBS4 gene was first reported as a likely non-disease causing variant (Mykytyn et al., 2003). In a more recent publication, Muller et al. (2010) identified K46R in the homozygous state in an individual diagnosed with Bardet-Biedl syndrome. A separate group performed functional studies in zebrafish by in vivo complementation analysis and predicted K46R is likely detrimental to the protein function (Zaghloul et al., 2010). However, K46R is reported as benign in ClinVar by a different clinical laboratory, but additional evidence is not available (ClinVar SCV000229244.1; Landrum et al., 2015). The NHLBI ESP Exome Sequencing Project reports K46R was observed in 1.02% (88/8594) alleles from individuals of European American ancestry, indicating it may be a rare variant in this population. The K46R variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret K46R as a variant of uncertain significance.
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000425800 SCV000511357 benign not provided 2016-07-08 criteria provided, single submitter clinical testing
Genetic Services Laboratory,University of Chicago RCV000177393 SCV000593601 likely benign not specified 2016-12-05 criteria provided, single submitter clinical testing
Invitae RCV001085083 SCV000636531 benign Bardet-Biedl syndrome 2019-12-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001119683 SCV001278113 benign Bardet-Biedl syndrome 4 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000709674 SCV000733470 likely benign Bardet-Biedl syndrome 1 no assertion criteria provided clinical testing

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