rs11637927
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The ENST00000395205.6(BBS4):c.-507C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0662 in 1,549,504 control chromosomes in the GnomAD database, including 3,973 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.047 ( 239 hom., cov: 32)
Exomes 𝑓: 0.068 ( 3734 hom. )
Consequence
BBS4
ENST00000395205.6 5_prime_UTR
ENST00000395205.6 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.77
Genes affected
BBS4 (HGNC:969): (Bardet-Biedl syndrome 4) This gene is a member of the Bardet-Biedl syndrome (BBS) gene family. Bardet-Biedl syndrome is an autosomal recessive disorder characterized by severe pigmentary retinopathy, obesity, polydactyly, renal malformation and cognitive disability. The proteins encoded by BBS gene family members are structurally diverse. The similar phenotypes exhibited by mutations in BBS gene family members are likely due to the protein's shared roles in cilia formation and function. Many BBS proteins localize to the basal bodies, ciliary axonemes, and pericentriolar regions of cells. BBS proteins may also be involved in intracellular trafficking via microtubule-related transport. The protein encoded by this gene has sequence similarity to O-linked N-acetylglucosamine (O-GlcNAc) transferases in plants and archaebacteria and in human forms a multi-protein "BBSome" complex with seven other BBS proteins. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]
HIGD2B (HGNC:26984): (HIG1 hypoxia inducible domain family member 2B) Predicted to be involved in mitochondrial respirasome assembly. Predicted to be integral component of membrane. Predicted to be active in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
Variant 15-72686190-C-A is Benign according to our data. Variant chr15-72686190-C-A is described in ClinVar as [Benign]. Clinvar id is 262133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-72686190-C-A is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0712 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HIGD2B | NM_001350932.3 | upstream_gene_variant | ENST00000311755.6 | ||||
BBS4 | NM_033028.5 | upstream_gene_variant | ENST00000268057.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BBS4 | ENST00000268057.9 | upstream_gene_variant | 1 | NM_033028.5 | P1 | ||||
HIGD2B | ENST00000311755.6 | upstream_gene_variant | 1 | NM_001350932.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0471 AC: 7164AN: 152216Hom.: 239 Cov.: 32
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GnomAD3 exomes AF: 0.0458 AC: 7214AN: 157460Hom.: 249 AF XY: 0.0453 AC XY: 3786AN XY: 83536
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GnomAD4 exome AF: 0.0683 AC: 95471AN: 1397170Hom.: 3734 Cov.: 30 AF XY: 0.0672 AC XY: 46327AN XY: 689498
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GnomAD4 genome ? AF: 0.0470 AC: 7163AN: 152334Hom.: 239 Cov.: 32 AF XY: 0.0453 AC XY: 3378AN XY: 74500
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Bardet-Biedl syndrome 4 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at