19-41006968-T-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The ENST00000324071.10(CYP2B6):c.548T>G(p.Val183Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as drug response (no stars).
Frequency
Genomes: not found (cov: 31)
Consequence
CYP2B6
ENST00000324071.10 missense
ENST00000324071.10 missense
Scores
10
5
4
Clinical Significance
Conservation
PhyloP100: 5.90
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 Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.909
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CYP2B6 | NM_000767.5 | c.548T>G | p.Val183Gly | missense_variant | 4/9 | ENST00000324071.10 | NP_000758.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CYP2B6 | ENST00000324071.10 | c.548T>G | p.Val183Gly | missense_variant | 4/9 | 1 | NM_000767.5 | ENSP00000324648 | P1 | |
CYP2B6 | ENST00000593831.1 | c.256+2522T>G | intron_variant | 2 | ENSP00000470582 | |||||
CYP2B6 | ENST00000594187.1 | n.132T>G | non_coding_transcript_exon_variant | 2/2 | 5 | |||||
CYP2B6 | ENST00000598834.2 | c.452T>G | p.Val151Gly | missense_variant, NMD_transcript_variant | 4/10 | 5 | ENSP00000496294 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD4 exome Cov.: 33
GnomAD4 exome
Cov.:
33
GnomAD4 genome Cov.: 31
GnomAD4 genome
Cov.:
31
ClinVar
Significance: drug response
Submissions summary: Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Efavirenz response Other:1
drug response, no assertion criteria provided | literature only | OMIM | May 15, 2015 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H;H
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Pathogenic
.;D
REVEL
Pathogenic
Sift
Pathogenic
.;D
Sift4G
Pathogenic
.;D
Polyphen
D;D
Vest4
0.62
MutPred
Loss of stability (P = 0.009);Loss of stability (P = 0.009);
MVP
0.92
MPC
0.45
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at