12-88049227-A-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_025114.4(CEP290):āc.7397T>Cā(p.Phe2466Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000561 in 1,604,486 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_025114.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CEP290 | NM_025114.4 | c.7397T>C | p.Phe2466Ser | missense_variant | 54/54 | ENST00000552810.6 | NP_079390.3 | |
RLIG1 | NM_001009894.3 | c.*805A>G | 3_prime_UTR_variant | 7/7 | ENST00000356891.4 | NP_001009894.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CEP290 | ENST00000552810.6 | c.7397T>C | p.Phe2466Ser | missense_variant | 54/54 | 1 | NM_025114.4 | ENSP00000448012.1 | ||
C12orf29 | ENST00000356891.4 | c.*805A>G | 3_prime_UTR_variant | 7/7 | 1 | NM_001009894.3 | ENSP00000349358.3 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 151964Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000415 AC: 1AN: 241128Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 130804
GnomAD4 exome AF: 0.00000482 AC: 7AN: 1452522Hom.: 0 Cov.: 29 AF XY: 0.00000416 AC XY: 3AN XY: 721818
GnomAD4 genome AF: 0.0000132 AC: 2AN: 151964Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74204
ClinVar
Submissions by phenotype
CEP290-related disorder Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 30, 2024 | The CEP290 c.7397T>C variant is predicted to result in the amino acid substitution p.Phe2466Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0030% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Leber congenital amaurosis Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Meckel-Gruber syndrome;C0431399:Familial aplasia of the vermis;C0687120:Nephronophthisis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 13, 2022 | This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 2466 of the CEP290 protein (p.Phe2466Ser). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with CEP290-related conditions. ClinVar contains an entry for this variant (Variation ID: 946983). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at