19-40991346-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_000767.5(CYP2B6):​c.41G>A​(p.Gly14Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000658 in 152,058 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Consequence

CYP2B6
NM_000767.5 missense

Scores

2
4
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.24
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.809

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CYP2B6NM_000767.5 linkc.41G>A p.Gly14Glu missense_variant Exon 1 of 9 ENST00000324071.10 NP_000758.1 P20813-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CYP2B6ENST00000324071.10 linkc.41G>A p.Gly14Glu missense_variant Exon 1 of 9 1 NM_000767.5 ENSP00000324648.2 P20813-1
CYP2B6ENST00000598834.2 linkn.-59G>A upstream_gene_variant 5 ENSP00000496294.1 A0A2R8YFA4

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152058
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152058
Hom.:
0
Cov.:
31
AF XY:
0.0000135
AC XY:
1
AN XY:
74264
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 12, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.41G>A (p.G14E) alteration is located in exon 1 (coding exon 1) of the CYP2B6 gene. This alteration results from a G to A substitution at nucleotide position 41, causing the glycine (G) at amino acid position 14 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.64
BayesDel_addAF
Uncertain
0.060
T
BayesDel_noAF
Benign
-0.15
CADD
Benign
19
DANN
Benign
0.82
DEOGEN2
Benign
0.044
T;T
Eigen
Benign
-0.063
Eigen_PC
Benign
-0.21
FATHMM_MKL
Benign
0.51
D
LIST_S2
Benign
0.34
.;T
M_CAP
Benign
0.0049
T
MetaRNN
Pathogenic
0.81
D;D
MetaSVM
Benign
-0.40
T
MutationAssessor
Benign
0.81
L;L
PrimateAI
Uncertain
0.56
T
PROVEAN
Uncertain
-3.7
.;D
REVEL
Uncertain
0.47
Sift
Benign
0.11
.;T
Sift4G
Benign
0.20
.;T
Polyphen
1.0
D;D
Vest4
0.54
MutPred
0.66
Gain of relative solvent accessibility (P = 0.09);Gain of relative solvent accessibility (P = 0.09);
MVP
0.82
MPC
0.083
ClinPred
0.73
D
GERP RS
3.1
Varity_R
0.15
gMVP
0.59

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1263464555; hg19: chr19-41497251; API