chr2-38068461-T-G
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_000104.4(CYP1B1):c.*2261A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00707 in 225,554 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0093 ( 18 hom., cov: 33)
Exomes 𝑓: 0.0025 ( 3 hom. )
Consequence
CYP1B1
NM_000104.4 3_prime_UTR
NM_000104.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0420
Genes affected
CYP1B1 (HGNC:2597): (cytochrome P450 family 1 subfamily B member 1) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. The enzyme encoded by this gene localizes to the endoplasmic reticulum and metabolizes procarcinogens such as polycyclic aromatic hydrocarbons and 17beta-estradiol. Mutations in this gene have been associated with primary congenital glaucoma; therefore it is thought that the enzyme also metabolizes a signaling molecule involved in eye development, possibly a steroid. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
Variant 2-38068461-T-G is Benign according to our data. Variant chr2-38068461-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 898036.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00925 (1409/152308) while in subpopulation AFR AF= 0.0287 (1194/41570). AF 95% confidence interval is 0.0274. There are 18 homozygotes in gnomad4. There are 702 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 18 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CYP1B1 | NM_000104.4 | c.*2261A>C | 3_prime_UTR_variant | 3/3 | ENST00000610745.5 | NP_000095.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CYP1B1 | ENST00000610745.5 | c.*2261A>C | 3_prime_UTR_variant | 3/3 | 1 | NM_000104.4 | ENSP00000478561 | P1 | ||
CYP1B1 | ENST00000490576.2 | c.*2261A>C | 3_prime_UTR_variant | 3/3 | 4 | ENSP00000478839 | P1 | |||
CYP1B1 | ENST00000491456.1 | n.184+717A>C | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.00924 AC: 1406AN: 152190Hom.: 18 Cov.: 33
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GnomAD4 exome AF: 0.00254 AC: 186AN: 73246Hom.: 3 Cov.: 0 AF XY: 0.00233 AC XY: 79AN XY: 33874
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GnomAD4 genome AF: 0.00925 AC: 1409AN: 152308Hom.: 18 Cov.: 33 AF XY: 0.00943 AC XY: 702AN XY: 74474
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Glaucoma 3A Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Irido-corneo-trabecular dysgenesis Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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