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GeneBe

rs2279343

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_000767.5(CYP2B6):c.785A>G(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. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.29 ( 6478 hom., cov: 25)
Exomes 𝑓: 0.16 ( 38948 hom. )
Failed GnomAD Quality Control

Consequence

CYP2B6
NM_000767.5 missense

Scores

13

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: 0.784
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0074420273).
BS2
High AC in GnomAdExome at 27016 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CYP2B6NM_000767.5 linkuse as main transcriptc.785A>G p.Lys262Arg missense_variant 5/9 ENST00000324071.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CYP2B6ENST00000324071.10 linkuse as main transcriptc.785A>G p.Lys262Arg missense_variant 5/91 NM_000767.5 P1P20813-1
CYP2B6ENST00000593831.1 linkuse as main transcriptc.257-2940A>G intron_variant 2
CYP2B6ENST00000598834.2 linkuse as main transcriptc.*226A>G 3_prime_UTR_variant, NMD_transcript_variant 6/105

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
42549
AN:
145088
Hom.:
6480
Cov.:
25
FAILED QC
Gnomad AFR
AF:
0.357
Gnomad AMI
AF:
0.123
Gnomad AMR
AF:
0.338
Gnomad ASJ
AF:
0.317
Gnomad EAS
AF:
0.272
Gnomad SAS
AF:
0.388
Gnomad FIN
AF:
0.224
Gnomad MID
AF:
0.326
Gnomad NFE
AF:
0.252
Gnomad OTH
AF:
0.308
GnomAD3 exomes
AF:
0.129
AC:
27016
AN:
208848
Hom.:
7469
AF XY:
0.129
AC XY:
14529
AN XY:
112738
show subpopulations
Gnomad AFR exome
AF:
0.171
Gnomad AMR exome
AF:
0.166
Gnomad ASJ exome
AF:
0.148
Gnomad EAS exome
AF:
0.147
Gnomad SAS exome
AF:
0.252
Gnomad FIN exome
AF:
0.0752
Gnomad NFE exome
AF:
0.0878
Gnomad OTH exome
AF:
0.150
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.164
AC:
187493
AN:
1142912
Hom.:
38948
Cov.:
36
AF XY:
0.173
AC XY:
98990
AN XY:
573654
show subpopulations
Gnomad4 AFR exome
AF:
0.271
Gnomad4 AMR exome
AF:
0.215
Gnomad4 ASJ exome
AF:
0.249
Gnomad4 EAS exome
AF:
0.226
Gnomad4 SAS exome
AF:
0.345
Gnomad4 FIN exome
AF:
0.192
Gnomad4 NFE exome
AF:
0.135
Gnomad4 OTH exome
AF:
0.197
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.293
AC:
42562
AN:
145210
Hom.:
6478
Cov.:
25
AF XY:
0.293
AC XY:
20728
AN XY:
70634
show subpopulations
Gnomad4 AFR
AF:
0.356
Gnomad4 AMR
AF:
0.338
Gnomad4 ASJ
AF:
0.317
Gnomad4 EAS
AF:
0.271
Gnomad4 SAS
AF:
0.386
Gnomad4 FIN
AF:
0.224
Gnomad4 NFE
AF:
0.252
Gnomad4 OTH
AF:
0.310
Alfa
AF:
0.251
Hom.:
1054
ExAC
AF:
0.0920
AC:
11067

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, no assertion criteria providedclinical testingDiagnostic Laboratory, Department of Genetics, University Medical Center Groningen-- -
Benign, criteria provided, single submitterclinical testingClinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical CenterAug 05, 2015- -
drug response, no assertion criteria providedliterature onlyOMIMMay 15, 2015- -
CYP2B6-related condition Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesJul 22, 2021This 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.057
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.68
Cadd
Benign
0.081
Dann
Benign
0.13
DEOGEN2
Benign
0.0015
T;T
Eigen
Benign
-1.8
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.012
N
MetaRNN
Benign
0.0074
T;T
MetaSVM
Benign
-0.90
T
MutationAssessor
Benign
-2.9
N;N
MutationTaster
Benign
1.0
P;P
PrimateAI
Benign
0.24
T
Polyphen
0.0
B;B
Vest4
0.021
MPC
0.057
ClinPred
0.0052
T
GERP RS
-1.7
Varity_R
0.055
gMVP
0.096

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs2279343; hg19: chr19-41515263; COSMIC: COSV57842539; COSMIC: COSV57842539; API