rs79859848
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_014704.4(CEP104):c.177G>A(p.Leu59=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00111 in 1,613,628 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0060 ( 11 hom., cov: 31)
Exomes 𝑓: 0.00060 ( 6 hom. )
Consequence
CEP104
NM_014704.4 synonymous
NM_014704.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.510
Genes affected
CEP104 (HGNC:24866): (centrosomal protein 104) This gene encodes a centrosomal protein required for ciliogenesis and for ciliary tip structural integrity. The mammalian protein contains three amino-terminal hydrophobic domains, two glycosylation sites, four cysteine-rich motifs, and two regions with homology to the glutamate receptor ionotropic, NMDA 1 protein. During ciliogenesis, the encoded protein translocates from the distal tips of the centrioles to the tip of the elongating cilium. Knockdown of the protein in human retinal pigment cells results in severe defects in ciliogenesis with structural deformities at the ciliary tips. Allelic variants of this gene are associated with the autosomal-recessive disorder Joubert syndrome, which is characterized by a distinctive mid-hindbrain and cerebellar malformation, oculomotor apraxia, irregular breathing, developmental delay, and ataxia. [provided by RefSeq, Feb 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
?
Variant 1-3848718-C-T is Benign according to our data. Variant chr1-3848718-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 475459.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.51 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00597 (909/152148) while in subpopulation AFR AF= 0.0204 (847/41502). AF 95% confidence interval is 0.0193. There are 11 homozygotes in gnomad4. There are 461 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 11 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CEP104 | NM_014704.4 | c.177G>A | p.Leu59= | synonymous_variant | 3/22 | ENST00000378230.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CEP104 | ENST00000378230.8 | c.177G>A | p.Leu59= | synonymous_variant | 3/22 | 5 | NM_014704.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00597 AC: 907AN: 152030Hom.: 11 Cov.: 31
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GnomAD3 exomes AF: 0.00153 AC: 385AN: 251106Hom.: 1 AF XY: 0.00118 AC XY: 160AN XY: 135732
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GnomAD4 exome AF: 0.000599 AC: 875AN: 1461480Hom.: 6 Cov.: 32 AF XY: 0.000539 AC XY: 392AN XY: 727050
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GnomAD4 genome ? AF: 0.00597 AC: 909AN: 152148Hom.: 11 Cov.: 31 AF XY: 0.00620 AC XY: 461AN XY: 74370
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Joubert syndrome 25 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 23, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 05, 2021 | - - |
CEP104-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 05, 2019 | 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). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
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