rs199770158
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_025114.4(CEP290):c.943-4C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00029 in 1,480,450 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_025114.4 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CEP290 | NM_025114.4 | c.943-4C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000552810.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CEP290 | ENST00000552810.6 | c.943-4C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_025114.4 | P4 |
Frequencies
GnomAD3 genomes AF: 0.000356 AC: 54AN: 151846Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000285 AC: 46AN: 161474Hom.: 0 AF XY: 0.000246 AC XY: 22AN XY: 89324
GnomAD4 exome AF: 0.000282 AC: 375AN: 1328486Hom.: 1 Cov.: 24 AF XY: 0.000306 AC XY: 202AN XY: 659504
GnomAD4 genome AF: 0.000355 AC: 54AN: 151964Hom.: 0 Cov.: 33 AF XY: 0.000350 AC XY: 26AN XY: 74274
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Feb 06, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2024 | CEP290: BP4 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 05, 2021 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia | Nov 16, 2015 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 11, 2021 | The c.943-4C>T intronic alteration consists of a C to T substitution 4 nucleotides before coding exon 11 in the CEP290 gene. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Meckel-Gruber syndrome;C0431399:Familial aplasia of the vermis;C0687120:Nephronophthisis Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2024 | - - |
CEP290-related ciliopathies Other:1
not provided, no classification provided | phenotyping only | GenomeConnect, ClinGen | - | GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at