ClinVar Miner

Submissions for variant NM_176824.3(BBS7):c.223A>G (p.Ile75Val)

gnomAD frequency: 0.00039  dbSNP: rs138872188
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000178402 SCV000230476 uncertain significance not provided 2015-03-05 criteria provided, single submitter clinical testing
Invitae RCV001068885 SCV001234018 uncertain significance Bardet-Biedl syndrome 2022-10-24 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 75 of the BBS7 protein (p.Ile75Val). This variant is present in population databases (rs138872188, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with BBS7-related conditions. ClinVar contains an entry for this variant (Variation ID: 197387). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BBS7 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.
Ambry Genetics RCV002517733 SCV003719518 uncertain significance Inborn genetic diseases 2022-01-31 criteria provided, single submitter clinical testing The c.223A>G (p.I75V) alteration is located in exon 4 (coding exon 4) of the BBS7 gene. This alteration results from a A to G substitution at nucleotide position 223, causing the isoleucine (I) at amino acid position 75 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Preventiongenetics, part of Exact Sciences RCV003398895 SCV004104693 uncertain significance BBS7-related condition 2023-06-14 criteria provided, single submitter clinical testing The BBS7 c.223A>G variant is predicted to result in the amino acid substitution p.Ile75Val. To our knowledge, this variant has not been reported in individuals with suspected Bardet-Biedl syndrome, although this variant was reported in a large cohort study of individuals with psoriasis (Table S3, reported as rs138872188, Yang et al. 2020. PubMed ID: 31376382). This variant is reported in 0.10% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/4-122782777-T-C), which is more common than expected for a primary cause of disease. Although we suspect this variant may be benign, at this time, the clinical significance is uncertain due to the absence of conclusive functional and genetic evidence.

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