rs55848325
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2
The NM_024649.5(BBS1):āc.24T>Cā(p.Asp8Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0039 in 1,614,192 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_024649.5 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00287 AC: 437AN: 152228Hom.: 2 Cov.: 32
GnomAD3 exomes AF: 0.00402 AC: 1009AN: 250784Hom.: 5 AF XY: 0.00425 AC XY: 577AN XY: 135676
GnomAD4 exome AF: 0.00400 AC: 5851AN: 1461846Hom.: 20 Cov.: 33 AF XY: 0.00417 AC XY: 3036AN XY: 727218
GnomAD4 genome AF: 0.00287 AC: 437AN: 152346Hom.: 2 Cov.: 32 AF XY: 0.00246 AC XY: 183AN XY: 74502
ClinVar
Submissions by phenotype
Bardet-Biedl syndrome 1 Uncertain:1Benign:4
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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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
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not specified Benign:4
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Variant summary: BBS1 c.24T>C alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0039 in 276810 control chromosomes in the gnomAD database, including 5 homozygotes. The observed variant frequency is approximately 4-fold of the estimated maximal expected allele frequency for a pathogenic variant in BBS1 causing Bardet-Biedl Syndrome phenotype (0.00094), strongly suggesting that the variant is benign. The variant, c.24T>C, has been reported in the literature in individuals affected with Bardet-Biedl Syndrome (Gerth_2008, Deveault_2011, Hichri_2005) but in some cases not all BBS genes were tested. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign. -
not provided Benign:2
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BBS1: BP4, BP7, BS2 -
BBS1-related disorder Benign:1
This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Bardet-Biedl syndrome Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at