rs4986893
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM4BP6_StrongBA1
The NM_000769(CYP2C19):c.636G>A(p.Trp212Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.00251 in 152056 control chromosomes in the gnomAD Genomes database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as drug response (β β β β ). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: π 0.0025 ( 11 hom., cov: 32)
Exomes π: 0.0054 ( 40 hom. )
Consequence
CYP2C19
NM_000769 stop_gained
NM_000769 stop_gained
Scores
1
1
5
Clinical Significance
Conservation
PhyloP100: 4.14
Links
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
PM4
?
Stoplost variant in NM_000769 Downstream stopcodon found after 498 codons.
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: {other=1, drug_response=1, Benign=1}. Variant chr10-94780653-G-A is described in Lovd as [Benign]. Variant chr10-94780653-G-A is described in Lovd as [Pathogenic].
BA1
?
GnomAd highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0555 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CYP2C19 | NM_000769.4 | c.636G>A | p.Trp212Ter | stop_gained | 4/9 | ENST00000371321.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYP2C19 | ENST00000371321.9 | c.636G>A | p.Trp212Ter | stop_gained | 4/9 | 1 | NM_000769.4 | 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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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
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
MutationTaster
Benign
A
Vest4
GERP RS
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at