rs35773040

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000767.5(CYP2B6):c.419G>A(p.Arg140Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00325 in 1,613,998 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0032 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0033 ( 17 hom. )

Consequence

CYP2B6
NM_000767.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.16

Publications

26 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0068762302).

BP6

Variant 19-41004381-G-A is Benign according to our data. Variant chr19-41004381-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2649918.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 492 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2B6	NM_000767.5 link	c.419G>A	p.Arg140Gln	missense_variant	Exon 3 of 9	ENST00000324071.10	NP_000758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
CYP2B6	ENST00000324071.10 link	c.419G>A	p.Arg140Gln	missense_variant	Exon 3 of 9	1	NM_000767.5	ENSP00000324648.2
CYP2B6	ENST00000593831.1 link	c.191G>A	p.Arg64Gln	missense_variant	Exon 2 of 5	2		ENSP00000470582.1
CYP2B6	ENST00000594187.1 link	n.3G>A		non_coding_transcript_exon_variant	Exon 1 of 2	5
CYP2B6	ENST00000598834.2 link	n.320G>A		non_coding_transcript_exon_variant	Exon 3 of 10	5		ENSP00000496294.1

Frequencies

GnomAD3 genomes

AF:

0.00325

AC:

494

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000363

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00354

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00435

Gnomad FIN

AF:

0.00565

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00485

Gnomad OTH

AF:

0.00431

GnomAD2 exomes

AF:

0.00314

AC:

789

AN:

251270

AF XY:

0.00335

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00168

Gnomad ASJ exome

AF:

0.000496

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00555

Gnomad NFE exome

AF:

0.00442

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00326

AC:

4761

AN:

1461804

Hom.:

Cov.:

AF XY:

0.00332

AC XY:

2416

AN XY:

727202

show subpopulations

African (AFR)

AF:

0.000388

AC:

AN:

33472

American (AMR)

AF:

0.00145

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.000497

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.00268

AC:

231

AN:

86226

European-Finnish (FIN)

AF:

0.00543

AC:

290

AN:

53394

Middle Eastern (MID)

AF:

0.000867

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00360

AC:

4008

AN:

1111994

Other (OTH)

AF:

0.00222

AC:

134

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

307

614

921

1228

1535

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

232

348

464

580

<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

AF:

0.00323

AC:

492

AN:

152194

Hom.:

Cov.:

AF XY:

0.00329

AC XY:

245

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.000362

AC:

AN:

41482

American (AMR)

AF:

0.00353

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.000864

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00414

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00565

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00485

AC:

330

AN:

68016

Other (OTH)

AF:

0.00426

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

112

140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00338

Hom.:

Bravo

AF:

0.00226

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00419

AC:

ExAC

AF:

0.00343

AC:

416

EpiCase

AF:

0.00294

EpiControl

AF:

0.00338

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CYP2B6: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.023

T;T;T

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.82

.;T;T

M_CAP

Benign

0.0050

MetaRNN

Benign

0.0069

T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.9

L;L;.

PhyloP100

1.2

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-2.5

.;N;.

REVEL

Benign

0.069

Sift

Benign

0.052

.;T;.

Sift4G

Benign

0.085

.;T;D

Polyphen

0.020

B;B;.

Vest4

0.22, 0.23

MVP

0.39

MPC

0.079

ClinPred

0.030

GERP RS

1.7

PromoterAI

0.0052

Neutral

(source)

Varity_R

0.36

gMVP

0.14

Mutation Taster

=90/10

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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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