2-38070996-T-C
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000104.4(CYP1B1):āc.1358A>Gā(p.Asn453Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.171 in 1,614,006 control chromosomes in the GnomAD database, including 25,836 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.13 ( 1623 hom., cov: 32)
Exomes š: 0.18 ( 24213 hom. )
Consequence
CYP1B1
NM_000104.4 missense
NM_000104.4 missense
Scores
7
7
Clinical Significance
Conservation
PhyloP100: 7.91
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0016258061).
BP6
?
Variant 2-38070996-T-C is Benign according to our data. Variant chr2-38070996-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 166969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-38070996-T-C is described in Lovd as [Benign]. Variant chr2-38070996-T-C is described in Lovd as [Pathogenic].
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CYP1B1 | NM_000104.4 | c.1358A>G | p.Asn453Ser | missense_variant | 3/3 | ENST00000610745.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYP1B1 | ENST00000610745.5 | c.1358A>G | p.Asn453Ser | missense_variant | 3/3 | 1 | NM_000104.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.130 AC: 19711AN: 152108Hom.: 1626 Cov.: 32
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GnomAD3 exomes AF: 0.153 AC: 38541AN: 251460Hom.: 3557 AF XY: 0.164 AC XY: 22275AN XY: 135908
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GnomAD4 exome AF: 0.175 AC: 256523AN: 1461780Hom.: 24213 Cov.: 33 AF XY: 0.178 AC XY: 129501AN XY: 727192
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GnomAD4 genome ? AF: 0.129 AC: 19705AN: 152226Hom.: 1623 Cov.: 32 AF XY: 0.129 AC XY: 9579AN XY: 74432
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:10
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Mar 03, 2014 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Dec 03, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Glaucoma 3A Benign:2
Likely benign, 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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 30, 2021 | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | This variant is associated with the following publications: (PMID: 15958554, 11854439, 15486049, 23861929, 10426814, 24604202) - |
Anterior segment dysgenesis 6 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 30, 2021 | - - |
Glaucoma 3, primary infantile, B;C1856439:Glaucoma 3A;C4310623:Anterior segment dysgenesis 6 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | May 12, 2022 | - - |
Congenital glaucoma Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;M
MutationTaster
Benign
P;P
PrimateAI
Benign
T
Sift4G
Uncertain
D;T;D
Vest4
ClinPred
T
GERP RS
Varity_R
gMVP
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