19-41004133-G-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_000767.5(CYP2B6):c.304G>T(p.Ala102Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000459 in 1,543,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 29)

Exomes 𝑓: 0.00049 ( 0 hom. )

Consequence

CYP2B6
NM_000767.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.380

Publications

4 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: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.090845704).

BS2

High AC in GnomAd4 at 18 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2B6	NM_000767.5 link	c.304G>T	p.Ala102Ser	missense_variant	Exon 2 of 9	ENST00000324071.10	NP_000758.1	P20813-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CYP2B6	ENST00000324071.10 link	c.304G>T	p.Ala102Ser	missense_variant	Exon 2 of 9	1	NM_000767.5	ENSP00000324648.2	P20813-1
CYP2B6	ENST00000593831.1 link	c.76G>T	p.Ala26Ser	missense_variant	Exon 1 of 5	2		ENSP00000470582.1	M0QZJ2
CYP2B6	ENST00000598834.2 link	n.205G>T		non_coding_transcript_exon_variant	Exon 2 of 10	5		ENSP00000496294.1	A0A2R8YFA4
CYP2B6	ENST00000594187.1 link	n.-246G>T		upstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000130

AC:

AN:

138874

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000267

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000258

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000915

AC:

AN:

251264

AF XY:

0.000103

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000185

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000492

AC:

691

AN:

1404986

Hom.:

Cov.:

AF XY:

0.000462

AC XY:

323

AN XY:

698688

show subpopulations

African (AFR)

AF:

0.0000314

AC:

AN:

31830

American (AMR)

AF:

0.00

AC:

AN:

43100

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24126

East Asian (EAS)

AF:

0.0000292

AC:

AN:

34276

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85816

European-Finnish (FIN)

AF:

0.0000208

AC:

AN:

47982

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5508

European-Non Finnish (NFE)

AF:

0.000628

AC:

676

AN:

1075676

Other (OTH)

AF:

0.000194

AC:

AN:

56672

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

109

145

181

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000130

AC:

AN:

138874

Hom.:

Cov.:

AF XY:

0.000105

AC XY:

AN XY:

66632

show subpopulations

African (AFR)

AF:

0.0000267

AC:

AN:

37484

American (AMR)

AF:

0.00

AC:

AN:

12458

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3378

East Asian (EAS)

AF:

0.00

AC:

AN:

4376

South Asian (SAS)

AF:

0.00

AC:

AN:

4146

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8164

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000258

AC:

AN:

65768

Other (OTH)

AF:

0.00

AC:

AN:

1926

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000160

Hom.:

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.0000824

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000296

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 10, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.304G>T (p.A102S) alteration is located in exon 2 (coding exon 2) of the CYP2B6 gene. This alteration results from a G to T substitution at nucleotide position 304, causing the alanine (A) at amino acid position 102 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.011

T;T;T

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.57

.;T;T

M_CAP

Benign

0.0089

MetaRNN

Benign

0.091

T;T;T

MetaSVM

Benign

-0.69

MutationAssessor

Benign

1.9

L;L;.

PhyloP100

0.38

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.8

.;N;.

REVEL

Benign

0.12

Sift

Uncertain

0.017

.;D;.

Sift4G

Uncertain

0.023

.;D;D

Polyphen

0.38

B;B;.

Vest4

0.055, 0.083

MVP

0.69

MPC

0.11

ClinPred

0.040

GERP RS

-0.97

PromoterAI

-0.097

Neutral

(source)

Varity_R

0.66

gMVP

0.30

Mutation Taster

=89/11

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

19-41004133-G-T

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