rs199476189
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_207352.4(CYP4V2):c.400G>T(p.Gly134Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000768 in 1,613,704 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
Consequence
NM_207352.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CYP4V2 | NM_207352.4 | c.400G>T | p.Gly134Ter | stop_gained | 3/11 | ENST00000378802.5 | |
CYP4V2 | XM_005262935.5 | c.400G>T | p.Gly134Ter | stop_gained | 3/11 | ||
CYP4V2 | XM_047450077.1 | c.18-865G>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYP4V2 | ENST00000378802.5 | c.400G>T | p.Gly134Ter | stop_gained | 3/11 | 1 | NM_207352.4 | P1 | |
CYP4V2 | ENST00000507209.5 | upstream_gene_variant | 1 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152190Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000203 AC: 51AN: 251400Hom.: 0 AF XY: 0.000199 AC XY: 27AN XY: 135880
GnomAD4 exome AF: 0.0000794 AC: 116AN: 1461514Hom.: 0 Cov.: 30 AF XY: 0.0000770 AC XY: 56AN XY: 727092
GnomAD4 genome AF: 0.0000526 AC: 8AN: 152190Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74356
ClinVar
Submissions by phenotype
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jul 19, 2022 | This variant is also known as c.704G>T. This premature translational stop signal has been observed in individual(s) with Bietti crystalline corneoretinal dystrophy (PMID: 15042513). This variant is present in population databases (rs199476189, gnomAD 0.04%). This sequence change creates a premature translational stop signal (p.Gly134*) 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). ClinVar contains an entry for this variant (Variation ID: 39265). For these reasons, this variant has been classified as Pathogenic. - |
Pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2018 | - - |
Bietti crystalline corneoretinal dystrophy Pathogenic:1
Pathogenic, no assertion criteria provided | curation | GeneReviews | Apr 12, 2012 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at