rs377613416
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong
The NM_025114.4(CEP290):c.6136-19T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000781 in 1,520,118 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00048 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00081 ( 1 hom. )
Consequence
CEP290
NM_025114.4 intron
NM_025114.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.470
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 -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant 12-88064134-A-C is Benign according to our data. Variant chr12-88064134-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 261850.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-88064134-A-C is described in Lovd as [Benign].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CEP290 | NM_025114.4 | c.6136-19T>G | intron_variant | ENST00000552810.6 | |||
LOC124902977 | XR_007063393.1 | n.886+7114A>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CEP290 | ENST00000552810.6 | c.6136-19T>G | intron_variant | 1 | NM_025114.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000480 AC: 73AN: 152124Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000424 AC: 59AN: 139076Hom.: 0 AF XY: 0.000408 AC XY: 30AN XY: 73446
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GnomAD4 exome AF: 0.000814 AC: 1114AN: 1367994Hom.: 1 Cov.: 26 AF XY: 0.000834 AC XY: 563AN XY: 674714
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GnomAD4 genome ? AF: 0.000480 AC: 73AN: 152124Hom.: 1 Cov.: 32 AF XY: 0.000404 AC XY: 30AN XY: 74298
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 14, 2016 | 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. - |
Likely 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
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 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