rs1166022838
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_024649.5(BBS1):c.17dup(p.Ser7IlefsTer9) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,836 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. S6S) has been classified as Likely benign.
Frequency
Consequence
NM_024649.5 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BBS1 | NM_024649.5 | c.17dup | p.Ser7IlefsTer9 | frameshift_variant | 1/17 | ENST00000318312.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BBS1 | ENST00000318312.12 | c.17dup | p.Ser7IlefsTer9 | frameshift_variant | 1/17 | 1 | NM_024649.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250766Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135684
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461836Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727212
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Bardet-Biedl syndrome 1 Pathogenic:1
Likely pathogenic, no assertion criteria provided | clinical testing | Counsyl | Sep 22, 2015 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Mar 17, 2021 | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Has not been previously published as pathogenic or benign to our knowledge - |
Retinal dystrophy Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Blueprint Genetics | Jan 03, 2019 | - - |
Bardet-Biedl syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 09, 2023 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 412283). This variant has not been reported in the literature in individuals affected with BBS1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Ser7Ilefs*9) in the BBS1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BBS1 are known to be pathogenic (PMID: 12118255, 21520335, 27032803). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at