chr2-38071052-C-T
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000104.4(CYP1B1):c.1302G>A(p.Trp434*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,688 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 (★).
Frequency
Consequence
NM_000104.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CYP1B1 | NM_000104.4 | c.1302G>A | p.Trp434* | stop_gained | Exon 3 of 3 | ENST00000610745.5 | NP_000095.2 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461688Hom.: 0 Cov.: 50 AF XY: 0.00 AC XY: 0AN XY: 727124
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Congenital glaucoma Pathogenic:1
A different truncation downstream of this variant (p.Asp449Metfs*8) has been determined to be pathogenic (PMID: 9497261, 27820421, 14635112, 12036985). This suggests that deletion of this region of the CYP1B1 protein is causative of disease. This variant has been reported in an individual affected with primary congenital glaucoma (PMID: 16735994). This sequence change results in a premature translational stop signal in the last exon of the CYP1B1 mRNA at codon 434 (p.Trp434*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 110 amino acids (~20%) of the CYP1B1 protein. 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