11-67458392-C-T
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_145200.5(CABP4):c.673C>T(p.Arg225*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,612,438 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_145200.5 stop_gained
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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CABP4 | NM_145200.5 | c.673C>T | p.Arg225* | stop_gained | 5/6 | ENST00000325656.7 | NP_660201.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CABP4 | ENST00000325656.7 | c.673C>T | p.Arg225* | stop_gained | 5/6 | 1 | NM_145200.5 | ENSP00000324960.5 | ||
CABP4 | ENST00000438189.6 | c.358C>T | p.Arg120* | stop_gained | 6/7 | 1 | ENSP00000401555.2 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152170Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000800 AC: 2AN: 250020Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135130
GnomAD4 exome AF: 0.00000959 AC: 14AN: 1460150Hom.: 0 Cov.: 31 AF XY: 0.00000689 AC XY: 5AN XY: 726152
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152288Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74462
ClinVar
Submissions by phenotype
Retinal dystrophy Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Blueprint Genetics | Jul 11, 2019 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg | Jan 01, 2019 | - - |
Cone-rod synaptic disorder, congenital nonprogressive Pathogenic:2
Pathogenic, no assertion criteria provided | clinical testing | Genomics England Pilot Project, Genomics England | - | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics, University of Leipzig Medical Center | Feb 14, 2018 | This variant was identified as homozygous - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 15, 2020 | This sequence change creates a premature translational stop signal (p.Arg225*) in the CABP4 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs531851447, ExAC 0.007%). This variant has been observed in individual(s) with cone-rod synaptic disorder (PMID: 28041643, 28341476, 29525873). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 438047). Loss-of-function variants in CABP4 are known to be pathogenic (PMID: 25307992). For these reasons, this variant has been classified as Pathogenic. - |
Cone dystrophy Pathogenic:1
Likely pathogenic, no assertion criteria provided | research | NIHR Bioresource Rare Diseases, University of Cambridge | Jan 01, 2015 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at