rs45482602

Positions:

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000767.5(CYP2B6):c.777C>A(p.Ser259Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00186 in 1,580,936 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0015 ( 1 hom., cov: 27)

Exomes 𝑓: 0.0019 ( 37 hom. )

Consequence

CYP2B6
NM_000767.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.55

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0068685114).

BP6

Variant 19-41009350-C-A is Benign according to our data. Variant chr19-41009350-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2649919.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-41009350-C-A is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd4 at 228 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2B6	NM_000767.5 link	c.777C>A	p.Ser259Arg	missense_variant	5/9	ENST00000324071.10	NP_000758.1	P20813-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CYP2B6	ENST00000324071.10 link	c.777C>A	p.Ser259Arg	missense_variant	5/9	1	NM_000767.5	ENSP00000324648.2	P20813-1
CYP2B6	ENST00000593831.1 link	c.257-2948C>A		intron_variant		2		ENSP00000470582.1	M0QZJ2
CYP2B6	ENST00000598834.2 link	n.*218C>A		non_coding_transcript_exon_variant	6/10	5		ENSP00000496294.1	A0A2R8YFA4
CYP2B6	ENST00000598834.2 link	n.*218C>A		3_prime_UTR_variant	6/10	5		ENSP00000496294.1	A0A2R8YFA4

Frequencies

GnomAD3 genomes

AF:

0.00151

AC:

228

AN:

150652

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000270

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00213

Gnomad ASJ

AF:

0.0118

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00171

Gnomad FIN

AF:

0.000383

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00181

Gnomad OTH

AF:

0.00145

GnomAD3 exomes

AF:

0.00248

AC:

609

AN:

245372

Hom.:

AF XY:

0.00266

AC XY:

353

AN XY:

132578

show subpopulations

Gnomad AFR exome

AF:

0.000459

Gnomad AMR exome

AF:

0.00176

Gnomad ASJ exome

AF:

0.0160

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00240

Gnomad FIN exome

AF:

0.000372

Gnomad NFE exome

AF:

0.00252

Gnomad OTH exome

AF:

0.00398

GnomAD4 exome

AF:

0.00190

AC:

2713

AN:

1430166

Hom.:

Cov.:

AF XY:

0.00197

AC XY:

1403

AN XY:

712156

show subpopulations

Gnomad4 AFR exome

AF:

0.000561

Gnomad4 AMR exome

AF:

0.00173

Gnomad4 ASJ exome

AF:

0.0155

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00218

Gnomad4 FIN exome

AF:

0.000169

Gnomad4 NFE exome

AF:

0.00161

Gnomad4 OTH exome

AF:

0.00294

GnomAD4 genome

AF:

0.00151

AC:

228

AN:

150770

Hom.:

Cov.:

AF XY:

0.00160

AC XY:

118

AN XY:

73588

show subpopulations

Gnomad4 AFR

AF:

0.000269

Gnomad4 AMR

AF:

0.00212

Gnomad4 ASJ

AF:

0.0118

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00171

Gnomad4 FIN

AF:

0.000383

Gnomad4 NFE

AF:

0.00181

Gnomad4 OTH

AF:

0.00143

Alfa

AF:

0.00248

Hom.:

Bravo

AF:

0.00181

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.00292

AC:

ExAC

AF:

0.00248

AC:

300

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2023

CYP2B6: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.64

CADD

Benign

2.5

DANN

Uncertain

0.99

DEOGEN2

Benign

0.014

T;T

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.055

LIST_S2

Benign

0.61

.;T

MetaRNN

Benign

0.0069

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

M;M

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-2.7

.;D

REVEL

Benign

0.081

Sift

Uncertain

0.026

.;D

Sift4G

Uncertain

0.046

.;D

Polyphen

1.0

D;D

Vest4

0.10

MutPred

0.16

Gain of solvent accessibility (P = 0.0155);Gain of solvent accessibility (P = 0.0155);

MVP

0.30

MPC

0.23

ClinPred

0.049

GERP RS

-3.3

Varity_R

0.70

gMVP

0.093

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over