rs964530890
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate
The NM_019098.5(CNGB3):c.1663-5T>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000215 in 1,396,956 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Consequence
NM_019098.5 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CNGB3 | NM_019098.5 | c.1663-5T>G | splice_region_variant, intron_variant | ENST00000320005.6 | NP_061971.3 | |||
CNGB3 | XM_011517138.3 | c.1249-5T>G | splice_region_variant, intron_variant | XP_011515440.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CNGB3 | ENST00000320005.6 | c.1663-5T>G | splice_region_variant, intron_variant | 1 | NM_019098.5 | ENSP00000316605.5 | ||||
CNGB3 | ENST00000681546.1 | n.1483-5T>G | splice_region_variant, intron_variant | |||||||
CNGB3 | ENST00000681746.1 | n.*74-5T>G | splice_region_variant, intron_variant | ENSP00000505959.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000215 AC: 3AN: 1396956Hom.: 0 Cov.: 23 AF XY: 0.00000143 AC XY: 1AN XY: 698986
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Achromatopsia 3 Pathogenic:1
Likely pathogenic, no assertion criteria provided | research | Molecular Genetics Laboratory, Institute for Ophthalmic Research | Mar 27, 2017 | - - |
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 09, 2021 | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Studies have shown that this variant is associated with altered splicing, but the impact on the resulting protein product is unknown (PMID: 16319819). ClinVar contains an entry for this variant (Variation ID: 427706). This variant has been observed in individual(s) with achromatopsia (PMID: 16319819, 28795510). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (ExAC no frequency). This sequence change falls in intron 14 of the CNGB3 gene. It does not directly change the encoded amino acid sequence of the CNGB3 protein. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at