rs149684063
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBS1_Supporting
The NM_207352.4(CYP4V2):āc.367A>Gā(p.Met123Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000421 in 1,614,092 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M123I) has been classified as Uncertain significance.
Frequency
Consequence
NM_207352.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CYP4V2 | NM_207352.4 | c.367A>G | p.Met123Val | missense_variant | 3/11 | ENST00000378802.5 | |
CYP4V2 | XM_005262935.5 | c.367A>G | p.Met123Val | missense_variant | 3/11 | ||
CYP4V2 | XM_047450077.1 | c.18-898A>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYP4V2 | ENST00000378802.5 | c.367A>G | p.Met123Val | missense_variant | 3/11 | 1 | NM_207352.4 | P1 | |
CYP4V2 | ENST00000507209.5 | upstream_gene_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.000276 AC: 42AN: 152216Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000792 AC: 199AN: 251406Hom.: 0 AF XY: 0.000758 AC XY: 103AN XY: 135890
GnomAD4 exome AF: 0.000436 AC: 638AN: 1461758Hom.: 0 Cov.: 30 AF XY: 0.000395 AC XY: 287AN XY: 727172
GnomAD4 genome ? AF: 0.000276 AC: 42AN: 152334Hom.: 0 Cov.: 33 AF XY: 0.000282 AC XY: 21AN XY: 74490
ClinVar
Submissions by phenotype
Bietti crystalline corneoretinal dystrophy Pathogenic:1Uncertain:3
Pathogenic, no assertion criteria provided | curation | GeneReviews | Apr 12, 2012 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | 3billion | Sep 01, 2022 | The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.074%). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with CYP4V2-related disorder (PMID: 15042513). However, the evidence of pathogenicity is insufficient at this time. Therefore, this variant is classified as uncertain significance according to the recommendation of ACMG/AMP guideline. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | The CYP4V2 c.367A>G (p.Met123Val) missense variant has been reported in a compound heterozygous state in one individual with Bietti crystalline dystrophy (Li et al. 2004). The p.Met123Val variant was absent from 100 controls but is reported at a frequency of 0.00496 in the East Asian population of the 1000 Genomes Project. The evidence for this variant is limited. The p.Met123Val variant is therefore classified as a variant of unknown significance but suspicious for pathogenicity for Bietti crystalline dystrophy. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. - |
Uncertain significance, criteria provided, single submitter | reference population | Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center | Mar 18, 2016 | - - |
not provided Uncertain:1Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Likely benign, no assertion criteria provided | literature only | Department of Ophthalmology and Visual Sciences Kyoto University | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2019 | - - |
Retinal dystrophy Pathogenic:1Uncertain:1
Likely pathogenic, criteria provided, single submitter | research | Dept Of Ophthalmology, Nagoya University | Oct 01, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Blueprint Genetics | Jul 03, 2019 | - - |
Corneal dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at