Genetic Variant NM_000767.5:c.296G>A (chr19-41004125-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_000767.5(CYP2B6):c.296G>A(p.Gly99Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00025 in 1,380,236 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00039 ( 1 hom., cov: 29)

Exomes 𝑓: 0.00024 ( 0 hom. )

Consequence

CYP2B6
NM_000767.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0860

Publications

27 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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008235216).

BS2

High AC in GnomAd4 at 47 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2B6	NM_000767.5 link	c.296G>A	p.Gly99Glu	missense_variant	Exon 2 of 9	ENST00000324071.10	NP_000758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
CYP2B6	ENST00000324071.10 link	c.296G>A	p.Gly99Glu	missense_variant	Exon 2 of 9	1	NM_000767.5	ENSP00000324648.2
CYP2B6	ENST00000593831.1 link	c.68G>A	p.Gly23Glu	missense_variant	Exon 1 of 5	2		ENSP00000470582.1
CYP2B6	ENST00000598834.2 link	n.197G>A		non_coding_transcript_exon_variant	Exon 2 of 10	5		ENSP00000496294.1

Frequencies

GnomAD3 genomes

AF:

0.000388

AC:

AN:

121080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000622

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00167

Gnomad ASJ

AF:

0.00699

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000959

Gnomad OTH

AF:

0.00122

GnomAD2 exomes

AF:

0.000438

AC:

110

AN:

251270

AF XY:

0.000427

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000521

Gnomad ASJ exome

AF:

0.00716

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000880

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.000237

AC:

298

AN:

1259110

Hom.:

Cov.:

AF XY:

0.000253

AC XY:

158

AN XY:

624072

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27614

American (AMR)

AF:

0.000544

AC:

AN:

38570

Ashkenazi Jewish (ASJ)

AF:

0.0100

AC:

189

AN:

18876

East Asian (EAS)

AF:

0.00

AC:

AN:

20856

South Asian (SAS)

AF:

0.00

AC:

AN:

84444

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35124

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4702

European-Non Finnish (NFE)

AF:

0.0000540

AC:

AN:

981750

Other (OTH)

AF:

0.000742

AC:

AN:

47174

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000388

AC:

AN:

121126

Hom.:

Cov.:

AF XY:

0.000411

AC XY:

AN XY:

55916

show subpopulations

African (AFR)

AF:

0.0000622

AC:

AN:

32162

American (AMR)

AF:

0.00167

AC:

AN:

8382

Ashkenazi Jewish (ASJ)

AF:

0.00699

AC:

AN:

3292

East Asian (EAS)

AF:

0.00

AC:

AN:

3640

South Asian (SAS)

AF:

0.00

AC:

AN:

3616

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4786

Middle Eastern (MID)

AF:

0.00

AC:

AN:

172

European-Non Finnish (NFE)

AF:

0.0000959

AC:

AN:

62556

Other (OTH)

AF:

0.00120

AC:

AN:

1662

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

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:

0.000356

Hom.:

Bravo

AF:

0.000366

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000371

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.53

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.048

T;T;T

Eigen

Benign

-0.095

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.84

.;T;T

M_CAP

Benign

0.0049

MetaRNN

Benign

0.0082

T;T;T

MetaSVM

Benign

-0.61

MutationAssessor

Uncertain

2.7

M;M;.

PhyloP100

0.086

PrimateAI

Benign

0.45

PROVEAN

Pathogenic

-5.7

.;D;.

REVEL

Benign

0.065

Sift

Uncertain

0.0040

.;D;.

Sift4G

Pathogenic

0.0010

.;D;D

Polyphen

1.0

D;D;.

Vest4

0.18, 0.18

MVP

0.61

MPC

0.45

ClinPred

0.23

GERP RS

1.6

PromoterAI

-0.0074

Neutral

(source)

Varity_R

0.89

gMVP

0.60

Mutation Taster

=83/17

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

Computational scores

Splicing

Publications

Other links and lift over