Variant rs36060847 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
CYP2B6	NM_000767.5 linkuse as main transcript	c.296G>A	p.Gly99Glu	missense_variant	2/9	ENST00000324071.10	NP_000758.1	P20813-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CYP2B6	ENST00000324071.10 linkuse as main transcript	c.296G>A	p.Gly99Glu	missense_variant	2/9	1	NM_000767.5	ENSP00000324648.2	P20813-1
CYP2B6	ENST00000593831.1 linkuse as main transcript	c.68G>A	p.Gly23Glu	missense_variant	1/5	2		ENSP00000470582.1	M0QZJ2
CYP2B6	ENST00000598834.2 linkuse as main transcript	n.197G>A		non_coding_transcript_exon_variant	2/10	5		ENSP00000496294.1	A0A2R8YFA4

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

GnomAD3 exomes

AF:

0.000438

AC:

110

AN:

251270

Hom.:

AF XY:

0.000427

AC XY:

AN XY:

135802

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 SAS 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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000544

Gnomad4 ASJ exome

AF:

0.0100

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000540

Gnomad4 OTH exome

AF:

0.000742

GnomAD4 genome

AF:

0.000388

AC:

AN:

121126

Hom.:

Cov.:

AF XY:

0.000411

AC XY:

AN XY:

55916

show subpopulations

Gnomad4 AFR

AF:

0.0000622

Gnomad4 AMR

AF:

0.00167

Gnomad4 ASJ

AF:

0.00699

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000959

Gnomad4 OTH

AF:

0.00120

Alfa

AF:

0.000644

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

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;.

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

Varity_R

0.89

gMVP

0.60

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over