chr11-66531684-A-AC
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_024649.5(BBS1):c.1642dupC(p.Leu548ProfsTer10) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
BBS1
NM_024649.5 frameshift
NM_024649.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.14
Publications
0 publications found
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]
ZDHHC24 (HGNC:27387): (zinc finger DHHC-type containing 24) Predicted to enable protein-cysteine S-palmitoyltransferase activity. Predicted to be involved in peptidyl-L-cysteine S-palmitoylation and protein targeting to membrane. Predicted to be integral component of membrane. Predicted to be active in Golgi apparatus and endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 12 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 11-66531684-A-AC is Pathogenic according to our data. Variant chr11-66531684-A-AC is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 3600129.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_024649.5. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| BBS1 | NM_024649.5 | MANE Select | c.1642dupC | p.Leu548ProfsTer10 | frameshift | Exon 16 of 17 | NP_078925.3 | ||
| ZDHHC24 | NM_001348571.2 | c.560-2197dupG | intron | N/A | NP_001335500.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| BBS1 | ENST00000318312.12 | TSL:1 MANE Select | c.1642dupC | p.Leu548ProfsTer10 | frameshift | Exon 16 of 17 | ENSP00000317469.7 | ||
| ENSG00000256349 | ENST00000419755.3 | TSL:2 | c.1753dupC | p.Leu585ProfsTer10 | frameshift | Exon 16 of 17 | ENSP00000398526.3 | ||
| BBS1 | ENST00000393994.4 | TSL:1 | c.1255dupC | p.Leu419ProfsTer10 | frameshift | Exon 13 of 13 | ENSP00000377563.2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461868Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727238 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1461868
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
727238
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33478
American (AMR)
AF:
AC:
0
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
AC:
0
AN:
53418
Middle Eastern (MID)
AF:
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1111994
Other (OTH)
AF:
AC:
0
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Bardet-Biedl syndrome 1 Pathogenic:1
May 01, 2024
Fulgent Genetics, Fulgent Genetics
Significance:Likely pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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