rs145094101
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate
The NM_024649.5(BBS1):āc.887T>Cā(p.Ile296Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000103 in 1,614,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I296V) has been classified as Uncertain significance.
Frequency
Consequence
NM_024649.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BBS1 | NM_024649.5 | c.887T>C | p.Ile296Thr | missense_variant | 10/17 | ENST00000318312.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BBS1 | ENST00000318312.12 | c.887T>C | p.Ile296Thr | missense_variant | 10/17 | 1 | NM_024649.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000184 AC: 28AN: 152064Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000915 AC: 23AN: 251480Hom.: 0 AF XY: 0.0000956 AC XY: 13AN XY: 135918
GnomAD4 exome AF: 0.0000951 AC: 139AN: 1461892Hom.: 0 Cov.: 31 AF XY: 0.000106 AC XY: 77AN XY: 727248
GnomAD4 genome ? AF: 0.000184 AC: 28AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.000229 AC XY: 17AN XY: 74386
ClinVar
Submissions by phenotype
Bardet-Biedl syndrome 1 Uncertain:3
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Apr 14, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Aug 20, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Apr 28, 2022 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 17, 2021 | The c.887T>C (p.I296T) alteration is located in exon 10 (coding exon 10) of the BBS1 gene. This alteration results from a T to C substitution at nucleotide position 887, causing the isoleucine (I) at amino acid position 296 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
BBS1-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 26, 2023 | The BBS1 c.887T>C variant is predicted to result in the amino acid substitution p.Ile296Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.064% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/11-66290983-T-C), which may be too common to be an undocumented disease causing variant. Although we suspect this variant may be benign, at this time its clinical significance is uncertain due to the absence of conclusive functional and genetic evidence. - |
Bardet-Biedl syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 18, 2022 | This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 296 of the BBS1 protein (p.Ile296Thr). This variant is present in population databases (rs145094101, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with BBS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 574647). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at