rs144109267
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PM2PP3_StrongPP5_Very_Strong
The NM_207352.4(CYP4V2):āc.1393A>Gā(p.Arg465Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,613,660 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 (ā ā ).
Frequency
Genomes: š 0.000013 ( 0 hom., cov: 32)
Exomes š: 0.000023 ( 0 hom. )
Consequence
CYP4V2
NM_207352.4 missense
NM_207352.4 missense
Scores
12
6
1
Clinical Significance
Conservation
PhyloP100: 2.47
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 14 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.982
PP5
?
Variant 4-186209260-A-G is Pathogenic according to our data. Variant chr4-186209260-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 166978.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-186209260-A-G is described in Lovd as [Pathogenic]. Variant chr4-186209260-A-G is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CYP4V2 | NM_207352.4 | c.1393A>G | p.Arg465Gly | missense_variant | 10/11 | ENST00000378802.5 | |
CYP4V2 | XM_005262935.5 | c.1390A>G | p.Arg464Gly | missense_variant | 10/11 | ||
CYP4V2 | XM_047450077.1 | c.997A>G | p.Arg333Gly | missense_variant | 8/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYP4V2 | ENST00000378802.5 | c.1393A>G | p.Arg465Gly | missense_variant | 10/11 | 1 | NM_207352.4 | P1 | |
CYP4V2 | ENST00000502665.1 | n.628A>G | non_coding_transcript_exon_variant | 4/5 | 1 | ||||
CYP4V2 | ENST00000507209.5 | n.6091A>G | non_coding_transcript_exon_variant | 5/6 | 1 | ||||
CYP4V2 | ENST00000513354.5 | n.483A>G | non_coding_transcript_exon_variant | 4/5 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 151780Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251428Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135896
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GnomAD4 exome AF: 0.0000226 AC: 33AN: 1461880Hom.: 0 Cov.: 36 AF XY: 0.0000193 AC XY: 14AN XY: 727240
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GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 151780Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74060
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 10, 2023 | This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 465 of the CYP4V2 protein (p.Arg465Gly). This variant is present in population databases (rs144109267, gnomAD 0.007%). This missense change has been observed in individuals with Bietti crystalline dystrophy (PMID: 23221965, 24480711, 25629076, 28051075, 29691984). ClinVar contains an entry for this variant (Variation ID: 166978). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CYP4V2 protein function. For these reasons, this variant has been classified as Pathogenic. - |
Pathogenic, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 11, 2014 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at