chr1-3815450-C-T
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_014704.4(CEP104):c.2730G>A(p.Pro910=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000545 in 1,613,318 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00016 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000044 ( 0 hom. )
Consequence
CEP104
NM_014704.4 synonymous
NM_014704.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.987
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 -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
?
Variant 1-3815450-C-T is Benign according to our data. Variant chr1-3815450-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2053647.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.987 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CEP104 | NM_014704.4 | c.2730G>A | p.Pro910= | synonymous_variant | 22/22 | ENST00000378230.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CEP104 | ENST00000378230.8 | c.2730G>A | p.Pro910= | synonymous_variant | 22/22 | 5 | NM_014704.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000158 AC: 24AN: 152200Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.000116 AC: 29AN: 249644Hom.: 0 AF XY: 0.000155 AC XY: 21AN XY: 135118
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GnomAD4 exome AF: 0.0000438 AC: 64AN: 1461000Hom.: 0 Cov.: 31 AF XY: 0.0000550 AC XY: 40AN XY: 726748
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GnomAD4 genome ? AF: 0.000158 AC: 24AN: 152318Hom.: 0 Cov.: 34 AF XY: 0.000161 AC XY: 12AN XY: 74496
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Joubert syndrome 25 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 08, 2022 | - - |
CEP104-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 05, 2020 | This variant is classified as likely 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
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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