rs2279343
Positions:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_000767.5(CYP2B6):āc.785A>Gā(p.Lys262Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.
Frequency
Genomes: š 0.29 ( 6478 hom., cov: 25)
Exomes š: 0.16 ( 38948 hom. )
Failed GnomAD Quality Control
Consequence
CYP2B6
NM_000767.5 missense
NM_000767.5 missense
Scores
13
Clinical Significance
Conservation
PhyloP100: 0.784
Genes affected
CYP2B6 (HGNC:2615): (cytochrome P450 family 2 subfamily B member 6) This gene, CYP2B6, 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 its expression is induced by phenobarbital. The enzyme is known to metabolize some xenobiotics, such as the anti-cancer drugs cyclophosphamide and ifosphamide. Transcript variants for this gene have been described; however, it has not been resolved whether these transcripts are in fact produced by this gene or by a closely related pseudogene, CYP2B7. Both the gene and the pseudogene are located in the middle of a CYP2A pseudogene found in a large cluster of cytochrome P450 genes from the CYP2A, CYP2B and CYP2F subfamilies on chromosome 19q. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0074420273).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CYP2B6 | NM_000767.5 | c.785A>G | p.Lys262Arg | missense_variant | 5/9 | ENST00000324071.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYP2B6 | ENST00000324071.10 | c.785A>G | p.Lys262Arg | missense_variant | 5/9 | 1 | NM_000767.5 | P1 | |
CYP2B6 | ENST00000593831.1 | c.257-2940A>G | intron_variant | 2 | |||||
CYP2B6 | ENST00000598834.2 | c.*226A>G | 3_prime_UTR_variant, NMD_transcript_variant | 6/10 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 42549AN: 145088Hom.: 6480 Cov.: 25 FAILED QC
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GnomAD3 exomes AF: 0.129 AC: 27016AN: 208848Hom.: 7469 AF XY: 0.129 AC XY: 14529AN XY: 112738
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.164 AC: 187493AN: 1142912Hom.: 38948 Cov.: 36 AF XY: 0.173 AC XY: 98990AN XY: 573654
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GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.293 AC: 42562AN: 145210Hom.: 6478 Cov.: 25 AF XY: 0.293 AC XY: 20728AN XY: 70634
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Efavirenz response Benign:2Other:1
Benign, criteria provided, single submitter | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | Aug 05, 2015 | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
drug response, no assertion criteria provided | literature only | OMIM | May 15, 2015 | - - |
CYP2B6-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 22, 2021 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N
MutationTaster
Benign
P;P
PrimateAI
Benign
T
Polyphen
B;B
Vest4
0.021
MPC
0.057
ClinPred
T
GERP RS
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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