chr1-3815608-C-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_014704.4(CEP104):c.2663-91G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 869,724 control chromosomes in the GnomAD database, including 152,647 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.65 ( 33236 hom., cov: 32)
Exomes 𝑓: 0.57 ( 119411 hom. )
Consequence
CEP104
NM_014704.4 intron
NM_014704.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.04
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
BP6
?
Variant 1-3815608-C-T is Benign according to our data. Variant chr1-3815608-C-T is described in ClinVar as [Benign]. Clinvar id is 1183590.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CEP104 | NM_014704.4 | c.2663-91G>A | intron_variant | ENST00000378230.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CEP104 | ENST00000378230.8 | c.2663-91G>A | intron_variant | 5 | NM_014704.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.646 AC: 98149AN: 151876Hom.: 33180 Cov.: 32
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GnomAD4 exome AF: 0.573 AC: 411582AN: 717730Hom.: 119411 AF XY: 0.577 AC XY: 210617AN XY: 364882
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GnomAD4 genome ? AF: 0.646 AC: 98263AN: 151994Hom.: 33236 Cov.: 32 AF XY: 0.647 AC XY: 48043AN XY: 74256
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Joubert syndrome 25 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 22, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 06, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Dann
Benign
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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