rs199476198
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_207352.4(CYP4V2):c.1020G>A(p.Trp340Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000274 in 1,461,892 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
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
CYP4V2
NM_207352.4 stop_gained
NM_207352.4 stop_gained
Scores
3
3
1
Clinical Significance
Conservation
PhyloP100: 5.23
Genes affected
CYP4V2 (HGNC:23198): (cytochrome P450 family 4 subfamily V member 2) This gene encodes a member of the cytochrome P450 hemethiolate protein superfamily which are involved in oxidizing various substrates in the metabolic pathway. It is implicated in the metabolism of fatty acid precursors into n-3 polyunsaturated fatty acids. Mutations in this gene result in Bietti crystalline corneoretinal dystrophy. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 4-186205232-G-A is Pathogenic according to our data. Variant chr4-186205232-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 39248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-186205232-G-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CYP4V2 | NM_207352.4 | c.1020G>A | p.Trp340Ter | stop_gained | 8/11 | ENST00000378802.5 | |
CYP4V2 | XM_005262935.5 | c.1020G>A | p.Trp340Ter | stop_gained | 8/11 | ||
CYP4V2 | XM_047450077.1 | c.624G>A | p.Trp208Ter | stop_gained | 6/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYP4V2 | ENST00000378802.5 | c.1020G>A | p.Trp340Ter | stop_gained | 8/11 | 1 | NM_207352.4 | P1 | |
CYP4V2 | ENST00000502665.1 | n.255G>A | non_coding_transcript_exon_variant | 2/5 | 1 | ||||
CYP4V2 | ENST00000507209.5 | n.5718G>A | non_coding_transcript_exon_variant | 3/6 | 1 | ||||
CYP4V2 | ENST00000513354.5 | n.110G>A | non_coding_transcript_exon_variant | 2/5 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251496Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135922
GnomAD3 exomes
AF:
AC:
1
AN:
251496
Hom.:
AF XY:
AC XY:
0
AN XY:
135922
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461892Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727248
GnomAD4 exome
AF:
AC:
4
AN:
1461892
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
727248
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
?
AF:
AC:
2
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
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 17, 2021 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 39248). This premature translational stop signal has been observed in individual(s) with CYP4V2-related conditions (PMID: 16088246, 28512305, 29785639). This variant is present in population databases (rs199476198, ExAC 0.02%). This sequence change creates a premature translational stop signal (p.Trp340*) in the CYP4V2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CYP4V2 are known to be pathogenic (PMID: 15042513, 25118264). - |
Retinal dystrophy Pathogenic:1
Pathogenic, criteria provided, single submitter | research | Dept Of Ophthalmology, Nagoya University | Oct 01, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AL_spliceai
Position offset: -32
Find out detailed SpliceAI scores and Pangolin per-transcript scores at