ClinVar Miner

Submissions for variant NM_152384.3(BBS5):c.143-1G>C

gnomAD frequency: 0.00004  dbSNP: rs1054138918
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000690428 SCV000818112 pathogenic Bardet-Biedl syndrome 2023-09-13 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 2 of the BBS5 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in BBS5 are known to be pathogenic (PMID: 15137946, 16877420, 26325687, 27708425, 28041643, 29806606). This variant is present in population databases (no rsID available, gnomAD 0.03%). ClinVar contains an entry for this variant (Variation ID: 569727). Disruption of this splice site has been observed in individual(s) with clinical features of Bardet-Biedl syndrome (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV000763466 SCV000894243 likely pathogenic Bardet-Biedl syndrome 5 2018-10-31 criteria provided, single submitter clinical testing
DBGen Ocular Genomics RCV000763466 SCV001737132 pathogenic Bardet-Biedl syndrome 5 2021-05-19 criteria provided, single submitter clinical testing
GeneDx RCV002281124 SCV002569559 likely pathogenic not provided 2022-03-03 criteria provided, single submitter clinical testing Canonical splice site variant expected to result in aberrant splicing, although in the absence of functional evidence the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 31589614, 34828430)
PreventionGenetics, part of Exact Sciences RCV003392526 SCV004120305 likely pathogenic BBS5-related condition 2024-02-14 criteria provided, single submitter clinical testing The BBS5 c.143-1G>C variant is predicted to disrupt the AG splice acceptor site and interfere with normal splicing. This variant has been reported in the homozygous state as well in the heterozygous state with a second pathogenic variant in individuals with inherited retinal disease (Villanueva-Mendoza et al. 2021. PubMed ID: 34828430). This variant was also reported in a large cohort study of individuals with Bardet-Biedl syndrome (Supp. Table 4 in Perea-Romero. 2022. PubMed ID: 35835773). This variant is reported in 0.029% of alleles in individuals of Latino descent in gnomAD. Variants that disrupt the consensus splice acceptor site in BBS5 are expected to be pathogenic and other protein termination variants upstream and downstream of this variant have been documented as causative (HGMD, ClinVar). This variant is interpreted as likely pathogenic.

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