rs199476203
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PM2PM5PP3_StrongPP5_Very_Strong
The NM_207352.4(CYP4V2):c.1199G>A(p.Arg400His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,614,140 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 Likely pathogenic (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R400C) has been classified as Likely pathogenic.
Frequency
Consequence
NM_207352.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CYP4V2 | NM_207352.4 | c.1199G>A | p.Arg400His | missense_variant | 9/11 | ENST00000378802.5 | |
CYP4V2 | XM_005262935.5 | c.1199G>A | p.Arg400His | missense_variant | 9/11 | ||
CYP4V2 | XM_047450077.1 | c.803G>A | p.Arg268His | missense_variant | 7/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYP4V2 | ENST00000378802.5 | c.1199G>A | p.Arg400His | missense_variant | 9/11 | 1 | NM_207352.4 | P1 | |
CYP4V2 | ENST00000502665.1 | n.434G>A | non_coding_transcript_exon_variant | 3/5 | 1 | ||||
CYP4V2 | ENST00000507209.5 | n.5897G>A | non_coding_transcript_exon_variant | 4/6 | 1 | ||||
CYP4V2 | ENST00000513354.5 | n.289G>A | non_coding_transcript_exon_variant | 3/5 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152130Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000636 AC: 16AN: 251488Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135918
GnomAD4 exome AF: 0.0000239 AC: 35AN: 1461892Hom.: 0 Cov.: 39 AF XY: 0.0000248 AC XY: 18AN XY: 727246
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152248Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74432
ClinVar
Submissions by phenotype
not provided Pathogenic:3
Likely pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2017 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 01, 2022 | For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CYP4V2 protein function. ClinVar contains an entry for this variant (Variation ID: 39254). This missense change has been observed in individual(s) with Bietti crystalline dystrophy and autosomal recessive retinitis pigmentosa (PMID: 16179904, 24480711, 28051075, 31960602). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs199476203, gnomAD 0.02%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 400 of the CYP4V2 protein (p.Arg400His). - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen | Oct 23, 2020 | - - |
Bietti crystalline corneoretinal dystrophy Pathogenic:2
Pathogenic, no assertion criteria provided | curation | GeneReviews | Apr 12, 2012 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | Mar 29, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at