rs2279343

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in 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

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O: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]

CYP2B6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0074420273).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2B6	NM_000767.5 link	c.785A>G	p.Lys262Arg	missense_variant	Exon 5 of 9	ENST00000324071.10	NP_000758.1	P20813-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CYP2B6	ENST00000324071.10 link	c.785A>G	p.Lys262Arg	missense_variant	Exon 5 of 9	1	NM_000767.5	ENSP00000324648.2	P20813-1
CYP2B6	ENST00000593831.1 link	c.257-2940A>G		intron_variant	Intron 2 of 4	2		ENSP00000470582.1	M0QZJ2
CYP2B6	ENST00000598834.2 link	n.*226A>G		non_coding_transcript_exon_variant	Exon 6 of 10	5		ENSP00000496294.1	A0A2R8YFA4
CYP2B6	ENST00000598834.2 link	n.*226A>G		3_prime_UTR_variant	Exon 6 of 10	5		ENSP00000496294.1	A0A2R8YFA4

Frequencies

GnomAD3 genomes

AF:

0.293

AC:

42549

AN:

145088

Hom.:

6480

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.129

AC:

27016

AN:

208848

AF XY:

0.129

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 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.:

AF XY:

0.173

AC XY:

98990

AN XY:

573654

show subpopulations

Gnomad4 AFR exome

AF:

0.271

AC:

6839

AN:

25198

Gnomad4 AMR exome

AF:

0.215

AC:

8136

AN:

37856

Gnomad4 ASJ exome

AF:

0.249

AC:

5470

AN:

21924

Gnomad4 EAS exome

AF:

0.226

AC:

8242

AN:

36392

Gnomad4 SAS exome

AF:

0.345

AC:

24676

AN:

71510

Gnomad4 FIN exome

AF:

0.192

AC:

9031

AN:

47084

Gnomad4 NFE exome

AF:

0.135

AC:

114515

AN:

849614

Gnomad4 Remaining exome

AF:

0.197

AC:

9617

AN:

48770

Heterozygous variant carriers

5628

11256

16883

22511

28139

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

2018

4036

6054

8072

10090

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.293

AC:

42562

AN:

145210

Hom.:

6478

Cov.:

AF XY:

0.293

AC XY:

20728

AN XY:

70634

show subpopulations

Gnomad4 AFR

AF:

0.356

AC:

0.356404

AN:

0.356404

Gnomad4 AMR

AF:

0.338

AC:

0.337728

AN:

0.337728

Gnomad4 ASJ

AF:

0.317

AC:

0.31703

AN:

0.31703

Gnomad4 EAS

AF:

0.271

AC:

0.270799

AN:

0.270799

Gnomad4 SAS

AF:

0.386

AC:

0.385649

AN:

0.385649

Gnomad4 FIN

AF:

0.224

AC:

0.223934

AN:

0.223934

Gnomad4 NFE

AF:

0.252

AC:

0.251961

AN:

0.251961

Gnomad4 OTH

AF:

0.310

AC:

0.310448

AN:

0.310448

Heterozygous variant carriers

1240

2480

3721

4961

6201

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

420

840

1260

1680

2100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.276

Hom.:

2155

ExAC

AF:

0.0920

AC:

11067

ClinVar

Significance: Benign

Submissions summary: Benign:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Efavirenz response

Benign:2Other:1

Aug 05, 2015

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

May 15, 2015

OMIM

Significance:drug response

Review Status:no assertion criteria provided

Collection Method:literature only

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

CYP2B6-related disorder

Benign:1

Jul 22, 2021

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.31

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

LIST_S2

Benign

0.50

.;T

MetaRNN

Benign

0.0074

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

-2.9

N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

1.9

.;N

REVEL

Benign

0.16

Sift

Benign

1.0

.;T

Sift4G

Benign

1.0

.;T

Polyphen

0.0

B;B

Vest4

0.021

MPC

0.057

ClinPred

0.0052

GERP RS

-1.7

Varity_R

0.055

gMVP

0.096

Mutation Taster

=100/0

polymorphism (auto)

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over