rs72549382
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_000104.4(CYP1B1):c.958G>T(p.Val320Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000128 in 1,613,308 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000104.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CYP1B1 | NM_000104.4 | c.958G>T | p.Val320Leu | missense_variant | Exon 2 of 3 | ENST00000610745.5 | NP_000095.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000131 AC: 20AN: 152176Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000310 AC: 77AN: 248424Hom.: 0 AF XY: 0.000259 AC XY: 35AN XY: 134908
GnomAD4 exome AF: 0.000128 AC: 187AN: 1461014Hom.: 1 Cov.: 31 AF XY: 0.000125 AC XY: 91AN XY: 726810
GnomAD4 genome AF: 0.000131 AC: 20AN: 152294Hom.: 0 Cov.: 33 AF XY: 0.000188 AC XY: 14AN XY: 74454
ClinVar
Submissions by phenotype
not specified Uncertain:1
Variant summary: CYP1B1 c.958G>T (p.Val320Leu) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00031 in 248424 control chromosomes, predominantly at a frequency of 0.0038 within the East Asian subpopulation in the gnomAD database. This frequency is not significantly higher than estimated for a pathogenic variant in CYP1B1 causing Primary Congenital Glaucoma (0.0038 vs 0.0043), allowing no conclusion about variant significance. c.958G>T has been reported in the literature, primarily in the heterozygous state, in individuals of East Asian ancestry affected with Primary Congenital Glaucoma (e.g. Mashima_2001, Kim_2011, Chen_2014, Do_2016), individuals with primary open-angle glaucoma (Gong_2015), and also in healthy controls (Kim_2011, Gong_2015). The variant was also found in the homozygous state in the unaffected mother of a heterozygous individual with Primary Congenital Glaucoma, providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 24227805, 26550974, 25527694, 21850185, 11527932, 12598442, 22942166). Four submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. -
Glaucoma 3, primary infantile, B;C1856439:Glaucoma 3A;C4310623:Anterior segment dysgenesis 6 Uncertain:1
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Glaucoma 3A Uncertain:1
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not provided Uncertain:1
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Congenital glaucoma Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at