rs4986893
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_StrongBA1
The NM_000769.4(CYP2C19):c.636G>A(p.Trp212Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.00294 in 1,613,588 control chromosomes in the GnomAD database, including 214 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as drug response (★★★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0025 ( 13 hom., cov: 32)
Exomes 𝑓: 0.0030 ( 201 hom. )
Consequence
CYP2C19
NM_000769.4 stop_gained
NM_000769.4 stop_gained
Scores
1
1
5
Clinical Significance
Conservation
PhyloP100: 4.14
Genes affected
CYP2C19 (HGNC:2621): (cytochrome P450 family 2 subfamily C member 19) 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. This protein localizes to the endoplasmic reticulum and is known to metabolize many xenobiotics, including the anticonvulsive drug mephenytoin, omeprazole, diazepam and some barbiturates. Polymorphism within this gene is associated with variable ability to metabolize mephenytoin, known as the poor metabolizer and extensive metabolizer phenotypes. The gene is located within a cluster of cytochrome P450 genes on chromosome 10q24. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP6
Variant 10-94780653-G-A is Benign according to our data. Variant chr10-94780653-G-A is described in ClinVar as [drug_response]. Clinvar id is 16899.Status of the report is practice_guideline, 4 stars. We mark this variant Likely_benign, oryginal submissions are: {drug_response=1, Benign=1, other=1}. Variant chr10-94780653-G-A is described in Lovd as [Benign]. Variant chr10-94780653-G-A is described in Lovd as [Pathogenic].
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0554 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CYP2C19 | NM_000769.4 | c.636G>A | p.Trp212Ter | stop_gained | 4/9 | ENST00000371321.9 | NP_000760.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CYP2C19 | ENST00000371321.9 | c.636G>A | p.Trp212Ter | stop_gained | 4/9 | 1 | NM_000769.4 | ENSP00000360372 | P1 | |
CYP2C19 | ENST00000645461.1 | n.1689G>A | non_coding_transcript_exon_variant | 3/7 |
Frequencies
GnomAD3 genomes AF: 0.00251 AC: 381AN: 152056Hom.: 11 Cov.: 32
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GnomAD3 exomes AF: 0.00538 AC: 1351AN: 251142Hom.: 40 AF XY: 0.00507 AC XY: 688AN XY: 135770
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GnomAD4 exome AF: 0.00298 AC: 4362AN: 1461412Hom.: 201 Cov.: 31 AF XY: 0.00303 AC XY: 2204AN XY: 727026
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GnomAD4 genome AF: 0.00255 AC: 388AN: 152176Hom.: 13 Cov.: 32 AF XY: 0.00273 AC XY: 203AN XY: 74362
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ClinVar
Significance: drug response
Submissions summary: Benign:1Other:5
Revision: practice guideline
LINK: link
Submissions by phenotype
not provided Benign:1Other:1
other, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 28, 2015 | - Variant classified as "other reportable" ??? variant is clinically benign (not associated with disease) but is reported when observed (e.g. pseudodeficiency alleles). |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 06, 2018 | This variant is associated with the following publications: (PMID: 22865819, 20549256, 21855977, 22344438, 25087612, 25525159, 23874401, 7969038, 24906606) - |
Proguanil, poor metabolism of Other:1
drug response, no assertion criteria provided | literature only | OMIM | Jun 01, 2009 | - - |
Mephenytoin, poor metabolism of Other:1
drug response, no assertion criteria provided | literature only | OMIM | Jun 01, 2009 | - - |
Acute coronary syndrome Other:1
drug response, no assertion criteria provided | research | Cardiology Department, The First Affiliated Hospital of Nanjing Medical University | - | - decreased function |
CYP2C19: no function Other:1
drug response, practice guideline | curation | Clinical Pharmacogenetics Implementation Consortium | - | - Allele function |
Computational scores
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Name
Calibrated prediction
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BayesDel_addAF
Benign
T
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
MutationTaster
Benign
A
Vest4
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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