rs45468703
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_025114.4(CEP290):c.297+36A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0205 in 1,072,728 control chromosomes in the GnomAD database, including 340 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.028 ( 78 hom., cov: 32)
Exomes 𝑓: 0.019 ( 262 hom. )
Consequence
CEP290
NM_025114.4 intron
NM_025114.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.823
Genes affected
CEP290 (HGNC:29021): (centrosomal protein 290) This gene encodes a protein with 13 putative coiled-coil domains, a region with homology to SMC chromosome segregation ATPases, six KID motifs, three tropomyosin homology domains and an ATP/GTP binding site motif A. The protein is localized to the centrosome and cilia and has sites for N-glycosylation, tyrosine sulfation, phosphorylation, N-myristoylation, and amidation. Mutations in this gene have been associated with Joubert syndrome and nephronophthisis and the presence of antibodies against this protein is associated with several forms of cancer. [provided by RefSeq, Jul 2008]
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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=-0.61).
BP6
?
Variant 12-88139109-T-C is Benign according to our data. Variant chr12-88139109-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 126254.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-88139109-T-C is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0281 (4277/152250) while in subpopulation AFR AF= 0.0501 (2081/41552). AF 95% confidence interval is 0.0483. There are 78 homozygotes in gnomad4. There are 2090 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 78 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CEP290 | NM_025114.4 | c.297+36A>G | intron_variant | ENST00000552810.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CEP290 | ENST00000552810.6 | c.297+36A>G | intron_variant | 1 | NM_025114.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0280 AC: 4266AN: 152132Hom.: 77 Cov.: 32
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GnomAD3 exomes AF: 0.0169 AC: 2810AN: 166694Hom.: 41 AF XY: 0.0157 AC XY: 1407AN XY: 89850
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GnomAD4 exome AF: 0.0192 AC: 17696AN: 920478Hom.: 262 Cov.: 12 AF XY: 0.0187 AC XY: 8848AN XY: 473754
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GnomAD4 genome ? AF: 0.0281 AC: 4277AN: 152250Hom.: 78 Cov.: 32 AF XY: 0.0281 AC XY: 2090AN XY: 74452
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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
not specified Benign:2
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 16, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
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