chr19-40991367-A-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_000767.5(CYP2B6):c.62A>T(p.Gln21Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00521 in 1,614,030 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0042 ( 3 hom., cov: 31)

Exomes 𝑓: 0.0053 ( 28 hom. )

Consequence

CYP2B6
NM_000767.5 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.149

Publications

14 publications found

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: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0040751696).

BP6

Variant 19-40991367-A-T is Benign according to our data. Variant chr19-40991367-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 3041988.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 641 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2B6	NM_000767.5 link	c.62A>T	p.Gln21Leu	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
CYP2B6	ENST00000324071.10 link	c.62A>T	p.Gln21Leu	missense_variant	Exon 1 of 9	1	NM_000767.5	ENSP00000324648.2		P20813-1
CYP2B6	ENST00000598834.2 link	n.-38A>T		upstream_gene_variant		5		ENSP00000496294.1		A0A2R8YFA4

Frequencies

GnomAD3 genomes

AF:

0.00422

AC:

641

AN:

152050

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000919

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.00956

Gnomad ASJ

AF:

0.00923

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00570

Gnomad OTH

AF:

0.00573

GnomAD2 exomes

AF:

0.00418

AC:

1052

AN:

251442

AF XY:

0.00432

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00416

Gnomad ASJ exome

AF:

0.00883

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.00616

Gnomad OTH exome

AF:

0.00619

GnomAD4 exome

AF:

0.00532

AC:

7775

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00523

AC XY:

3805

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.00117

AC:

AN:

33472

American (AMR)

AF:

0.00434

AC:

194

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00853

AC:

223

AN:

26134

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39698

South Asian (SAS)

AF:

0.00199

AC:

172

AN:

86254

European-Finnish (FIN)

AF:

0.000356

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00798

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00610

AC:

6784

AN:

1112000

Other (OTH)

AF:

0.00490

AC:

296

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

486

972

1459

1945

2431

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00421

AC:

641

AN:

152166

Hom.:

Cov.:

AF XY:

0.00390

AC XY:

290

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.000916

AC:

AN:

41480

American (AMR)

AF:

0.00955

AC:

146

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00923

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5182

South Asian (SAS)

AF:

0.00145

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.0000943

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.0171

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00571

AC:

388

AN:

68004

Other (OTH)

AF:

0.00567

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

100

134

167

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00591

Hom.:

Bravo

AF:

0.00458

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00545

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00500

AC:

ExAC

AF:

0.00385

AC:

468

EpiCase

AF:

0.00747

EpiControl

AF:

0.00907

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CYP2B6-related disorder

Benign:1

May 09, 2019

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

0.13

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.47

CADD

Benign

0.31

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.0084

T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.29

.;T

MetaRNN

Benign

0.0041

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N

PhyloP100

0.15

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.6

.;N

REVEL

Benign

0.16

Sift

Benign

0.088

.;T

Sift4G

Benign

0.64

.;T

Polyphen

0.011

B;B

Vest4

0.19

MVP

0.37

MPC

0.067

ClinPred

0.0027

GERP RS

-4.5

PromoterAI

-0.012

Neutral

(source)

Varity_R

0.049

gMVP

0.36

Mutation Taster

=98/2

polymorphism

(source)

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

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chr19-40991367-A-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over