rs7973969
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_025114.4(CEP290):c.5709+18C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00894 in 1,597,158 control chromosomes in the GnomAD database, including 1,174 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.049 ( 633 hom., cov: 32)
Exomes 𝑓: 0.0047 ( 541 hom. )
Consequence
CEP290
NM_025114.4 intron
NM_025114.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.344
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=-0.84).
BP6
?
Variant 12-88077204-G-T is Benign according to our data. Variant chr12-88077204-G-T is described in ClinVar as [Benign]. Clinvar id is 126263.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-88077204-G-T is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CEP290 | NM_025114.4 | c.5709+18C>A | intron_variant | ENST00000552810.6 | |||
LOC124902977 | XR_007063393.1 | n.887-5109G>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CEP290 | ENST00000552810.6 | c.5709+18C>A | intron_variant | 1 | NM_025114.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0494 AC: 7503AN: 151888Hom.: 632 Cov.: 32
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GnomAD3 exomes AF: 0.0120 AC: 2841AN: 236888Hom.: 233 AF XY: 0.00891 AC XY: 1146AN XY: 128576
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GnomAD4 exome AF: 0.00468 AC: 6760AN: 1445152Hom.: 541 Cov.: 30 AF XY: 0.00404 AC XY: 2900AN XY: 718360
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GnomAD4 genome ? AF: 0.0494 AC: 7515AN: 152006Hom.: 633 Cov.: 32 AF XY: 0.0476 AC XY: 3534AN XY: 74318
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 30, 2014 | 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. - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 27, 2015 | - - |
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 | - | - - |
Meckel-Gruber syndrome;C0431399:Familial aplasia of the vermis;C0687120:Nephronophthisis Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
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