11-66510683-T-C
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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.Asp8=) 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
Genomes: š 0.0029 ( 2 hom., cov: 32)
Exomes š: 0.0040 ( 20 hom. )
Consequence
BBS1
NM_024649.5 synonymous
NM_024649.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.04
Genes affected
BBS1 (HGNC:966): (Bardet-Biedl syndrome 1) Mutations in this gene have been observed in patients with the major form (type 1) of Bardet-Biedl syndrome. The encoded protein may play a role in eye, limb, cardiac and reproductive system development. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.65).
BP6
Variant 11-66510683-T-C is Benign according to our data. Variant chr11-66510683-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 193457.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=4, Uncertain_significance=1, Benign=4}. Variant chr11-66510683-T-C is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=2.04 with no splicing effect.
BS2
High Homozygotes in GnomAd4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BBS1 | NM_024649.5 | c.24T>C | p.Asp8= | synonymous_variant | 1/17 | ENST00000318312.12 | NP_078925.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BBS1 | ENST00000318312.12 | c.24T>C | p.Asp8= | synonymous_variant | 1/17 | 1 | NM_024649.5 | ENSP00000317469 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00287 AC: 437AN: 152228Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.00402 AC: 1009AN: 250784Hom.: 5 AF XY: 0.00425 AC XY: 577AN XY: 135676
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GnomAD4 exome AF: 0.00400 AC: 5851AN: 1461846Hom.: 20 Cov.: 33 AF XY: 0.00417 AC XY: 3036AN XY: 727218
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GnomAD4 genome AF: 0.00287 AC: 437AN: 152346Hom.: 2 Cov.: 32 AF XY: 0.00246 AC XY: 183AN XY: 74502
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:12
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Bardet-Biedl syndrome 1 Uncertain:1Benign:4
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | New York Genome Center | Mar 21, 2021 | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | Apr 19, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | Feb 25, 2015 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | 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. - |
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Sep 10, 2018 | 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. - |
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Sep 25, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 03, 2015 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2024 | BBS1: BP4, BP7, BS2 - |
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
BBS1-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 21, 2023 | 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
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at