Variant chr19-41006967-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000324071.10(CYP2B6):c.547G>A(p.Val183Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00477 in 1,613,900 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V183G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0035 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0049 ( 33 hom. )

Consequence

CYP2B6
ENST00000324071.10 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.82

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=0.016809613).

BS2

High AC in GnomAd4 at 526 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2B6	NM_000767.5 linkuse as main transcript	c.547G>A	p.Val183Ile	missense_variant	4/9	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.547G>A	p.Val183Ile	missense_variant	4/9	1	NM_000767.5	ENSP00000324648	P1	P20813-1
CYP2B6	ENST00000593831.1 linkuse as main transcript	c.256+2521G>A		intron_variant		2		ENSP00000470582
CYP2B6	ENST00000594187.1 linkuse as main transcript	n.131G>A		non_coding_transcript_exon_variant	2/2	5
CYP2B6	ENST00000598834.2 linkuse as main transcript	c.451G>A	p.Val151Ile	missense_variant, NMD_transcript_variant	4/10	5		ENSP00000496294

Frequencies

GnomAD3 genomes

AF:

0.00347

AC:

527

AN:

151970

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00237

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00243

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00179

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00519

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00326

AC:

820

AN:

251438

Hom.:

AF XY:

0.00307

AC XY:

417

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.00209

Gnomad AMR exome

AF:

0.00231

Gnomad ASJ exome

AF:

0.00338

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00121

Gnomad FIN exome

AF:

0.00125

Gnomad NFE exome

AF:

0.00516

Gnomad OTH exome

AF:

0.00342

GnomAD4 exome

AF:

0.00490

AC:

7167

AN:

1461812

Hom.:

Cov.:

AF XY:

0.00479

AC XY:

3486

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.00182

Gnomad4 AMR exome

AF:

0.00253

Gnomad4 ASJ exome

AF:

0.00310

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00109

Gnomad4 FIN exome

AF:

0.00144

Gnomad4 NFE exome

AF:

0.00585

Gnomad4 OTH exome

AF:

0.00383

GnomAD4 genome

AF:

0.00346

AC:

526

AN:

152088

Hom.:

Cov.:

AF XY:

0.00339

AC XY:

252

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.00237

Gnomad4 AMR

AF:

0.00242

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00179

Gnomad4 NFE

AF:

0.00518

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00449

Hom.:

Bravo

AF:

0.00345

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00467

AC:

ESP6500AA

AF:

0.00272

AC:

ESP6500EA

AF:

0.00488

AC:

ExAC

AF:

0.00325

AC:

394

EpiCase

AF:

0.00436

EpiControl

AF:

0.00539

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Benign

0.68

DEOGEN2

Benign

0.0053

T;T

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.17

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.62

.;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.017

T;T

MetaSVM

Benign

-0.83

MutationAssessor

Benign

1.8

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.75

.;N

REVEL

Benign

0.23

Sift

Benign

0.39

.;T

Sift4G

Benign

0.39

.;T

Polyphen

0.0020

B;B

Vest4

0.34

MVP

0.60

MPC

0.069

ClinPred

0.0094

GERP RS

4.5

Varity_R

0.23

gMVP

0.061

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