rs2279343

Positions:

Variant summary

Our verdict is Likely benign. Variant got -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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as 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

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 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	Protein	UniProt
CYP2B6	NM_000767.5 linkuse as main transcript	c.785A>G	p.Lys262Arg	missense_variant	5/9	ENST00000324071.10	NP_000758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2B6	ENST00000324071.10 linkuse as main transcript	c.785A>G	p.Lys262Arg	missense_variant	5/9	1	NM_000767.5	ENSP00000324648	P1	P20813-1
CYP2B6	ENST00000593831.1 linkuse as main transcript	c.257-2940A>G		intron_variant		2		ENSP00000470582
CYP2B6	ENST00000598834.2 linkuse as main transcript	c.*226A>G		3_prime_UTR_variant, NMD_transcript_variant	6/10	5		ENSP00000496294

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

42549

AN:

145088

Hom.:

6480

Cov.:

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.:

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.:

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

Submissions summary: Benign:4Other: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	- -
drug response, no assertion criteria provided	literature only	OMIM	May 15, 2015	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

CYP2B6-related disorder

Benign:1

Likely benign, no assertion criteria provided

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: 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

MutationTaster

Benign

1.0

P;P

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

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