rs199476182
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PVS1PM2PP3_StrongPP5_Moderate
The NM_207352.4(CYP4V2):c.327+1G>A variant causes a splice donor change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,386 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Consequence
NM_207352.4 splice_donor
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.327+1G>A | splice_donor_variant | ENST00000378802.5 | |||
CYP4V2 | XM_005262935.5 | c.327+1G>A | splice_donor_variant | ||||
CYP4V2 | XM_047450077.1 | c.17+1G>A | splice_donor_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYP4V2 | ENST00000378802.5 | c.327+1G>A | splice_donor_variant | 1 | NM_207352.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 6.86e-7 AC: 1AN: 1457386Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 725336
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Bietti crystalline corneoretinal dystrophy Pathogenic:1
Pathogenic, no assertion criteria provided | curation | GeneReviews | Apr 12, 2012 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 20, 2021 | This sequence change affects a donor splice site in intron 2 of the CYP4V2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CYP4V2 are known to be pathogenic (PMID: 15042513, 25118264). This variant is not present in population databases (ExAC no frequency). Disruption of this splice site has been observed in individual(s) with Bietti crystalline corneoretinal dystrophy (PMID: 15042513, 27658286, 28763560). ClinVar contains an entry for this variant (Variation ID: 39262). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at