Variant 19-41004158-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_000767.5(CYP2B6):c.329G>T(p.Gly110Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000169 in 989,700 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as drug response (no stars).

Frequency

Genomes: 𝑓 0.00067 ( 0 hom., cov: 28)

Exomes 𝑓: 0.000092 ( 0 hom. )

Consequence

CYP2B6
NM_000767.5 missense

Scores

Clinical Significance

drug response no assertion criteria provided O:1

Conservation

PhyloP100: 2.56

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 made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 88 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2B6	NM_000767.5 linkuse as main transcript	c.329G>T	p.Gly110Val	missense_variant	2/9	ENST00000324071.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2B6	ENST00000324071.10 linkuse as main transcript	c.329G>T	p.Gly110Val	missense_variant	2/9	1	NM_000767.5	P1	P20813-1
CYP2B6	ENST00000593831.1 linkuse as main transcript	c.101G>T	p.Gly34Val	missense_variant	1/5	2
CYP2B6	ENST00000598834.2 linkuse as main transcript	c.233G>T	p.Gly78Val	missense_variant, NMD_transcript_variant	2/10	5

Frequencies

GnomAD3 genomes

AF:

0.000658

AC:

AN:

130790

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00237

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000864

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000136

AC:

AN:

250694

Hom.:

AF XY:

0.000111

AC XY:

AN XY:

135658

show subpopulations

Gnomad AFR exome

AF:

0.00162

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000920

AC:

AN:

858796

Hom.:

Cov.:

AF XY:

0.000105

AC XY:

AN XY:

438762

show subpopulations

Gnomad4 AFR exome

AF:

0.00259

Gnomad4 AMR exome

AF:

0.000135

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000655

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000798

Gnomad4 OTH exome

AF:

0.000340

GnomAD4 genome

AF:

0.000672

AC:

AN:

130904

Hom.:

Cov.:

AF XY:

0.000822

AC XY:

AN XY:

62016

show subpopulations

Gnomad4 AFR

AF:

0.00242

Gnomad4 AMR

AF:

0.0000863

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000287

Hom.:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000140

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: drug response

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Efavirenz response

Other:1

drug response, no assertion criteria provided

literature only

OMIM

May 15, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.65

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.13

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.042

T;T;T

Eigen

Uncertain

0.26

Eigen_PC

Benign

0.0021

FATHMM_MKL

Uncertain

0.96

M_CAP

Benign

0.013

MetaRNN

Benign

0.10

T;T;T

MetaSVM

Uncertain

0.11

MutationAssessor

Pathogenic

3.3

M;M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.51

Polyphen

0.97

D;D;.

Vest4

0.64, 0.61

MVP

0.80

MPC

0.38

ClinPred

0.47

GERP RS

1.9

Varity_R

0.86

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.37

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.37

Position offset: -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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over