rs786205852
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_145200.5(CABP4):c.81_82insA(p.Pro28ThrfsTer4) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,454,110 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. TP27T?) has been classified as Pathogenic.
Frequency
Consequence
NM_145200.5 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CABP4 | NM_145200.5 | c.81_82insA | p.Pro28ThrfsTer4 | frameshift_variant | 1/6 | ENST00000325656.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CABP4 | ENST00000325656.7 | c.81_82insA | p.Pro28ThrfsTer4 | frameshift_variant | 1/6 | 1 | NM_145200.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 0.00000138 AC: 2AN: 1454110Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 722678
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Cone-rod synaptic disorder, congenital nonprogressive Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | Mar 29, 2024 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 01, 2013 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Apr 14, 2020 | Haplotype analysis of eleven affected individuals from four consanguineous Saudi Arabian families suggests this is a common founder mutation in this population (Khan et al., 2013); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 32552793, 25307992, 20157620, 23099293, 28635425, 19956407, 24332535, 23105016) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at