ClinVar Miner

Submissions for variant NM_033028.5(BBS4):c.437T>C (p.Ile146Thr)

gnomAD frequency: 0.00006  dbSNP: rs769886837
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001373221 SCV001569926 uncertain significance Bardet-Biedl syndrome 2022-07-19 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 146 of the BBS4 protein (p.Ile146Thr). This variant is present in population databases (rs769886837, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with BBS4-related conditions. ClinVar contains an entry for this variant (Variation ID: 1063389). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Fulgent Genetics, Fulgent Genetics RCV002493900 SCV002790569 uncertain significance Bardet-Biedl syndrome 4 2022-05-18 criteria provided, single submitter clinical testing
New York Genome Center RCV002493900 SCV003925378 uncertain significance Bardet-Biedl syndrome 4 2022-03-25 criteria provided, single submitter clinical testing
Breakthrough Genomics, Breakthrough Genomics RCV004692669 SCV005193917 uncertain significance not provided criteria provided, single submitter not provided
Ambry Genetics RCV004968150 SCV005544389 uncertain significance Inborn genetic diseases 2024-09-05 criteria provided, single submitter clinical testing The c.437T>C (p.I146T) alteration is located in exon 7 (coding exon 7) of the BBS4 gene. This alteration results from a T to C substitution at nucleotide position 437, causing the isoleucine (I) at amino acid position 146 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV004749671 SCV005346675 uncertain significance BBS4-related disorder 2024-07-23 no assertion criteria provided clinical testing The BBS4 c.437T>C variant is predicted to result in the amino acid substitution p.Ile146Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.012% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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