chr19-41004161-A-G

Position:

chr19-41004161-A-G

Variant summary

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

The NM_000767.5(CYP2B6):c.332A>G(p.Tyr111Cys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000344 in 958,204 control chromosomes in the GnomAD database, with no homozygous occurrence. 14/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., cov: 25)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

CYP2B6
NM_000767.5 missense, splice_region

Scores

Splicing: ADA: 0.005061

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.943

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 GnomAdExome4 at 31 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2B6	NM_000767.5 linkuse as main transcript	c.332A>G	p.Tyr111Cys	missense_variant, splice_region_variant	2/9	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.332A>G	p.Tyr111Cys	missense_variant, splice_region_variant	2/9	1	NM_000767.5	ENSP00000324648	P1	P20813-1
CYP2B6	ENST00000593831.1 linkuse as main transcript	c.104A>G	p.Tyr35Cys	missense_variant, splice_region_variant	1/5	2		ENSP00000470582
CYP2B6	ENST00000598834.2 linkuse as main transcript	c.236A>G	p.Tyr79Cys	missense_variant, splice_region_variant, NMD_transcript_variant	2/10	5		ENSP00000496294

Frequencies

GnomAD3 genomes

AF:

0.0000184

AC:

AN:

108522

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000360

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:

0.0000171

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000798

AC:

AN:

250682

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135656

show subpopulations

Gnomad AFR exome

AF:

0.0000624

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000365

AC:

AN:

849682

Hom.:

Cov.:

AF XY:

0.0000278

AC XY:

AN XY:

430934

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000305

Gnomad4 NFE exome

AF:

0.0000470

Gnomad4 OTH exome

AF:

0.0000312

GnomAD4 genome

AF:

0.0000184

AC:

AN:

108522

Hom.:

Cov.:

AF XY:

0.0000203

AC XY:

AN XY:

49218

show subpopulations

Gnomad4 AFR

AF:

0.0000360

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000171

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000740

Hom.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 20, 2023

The c.332A>G (p.Y111C) alteration is located in exon 2 (coding exon 2) of the CYP2B6 gene. This alteration results from a A to G substitution at nucleotide position 332, causing the tyrosine (Y) at amino acid position 111 to be replaced by a cysteine (C). 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

0.18

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.043

T;T;T

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.32

.;T;T

M_CAP

Benign

0.015

MetaRNN

Uncertain

0.48

T;T;T

MetaSVM

Benign

-0.58

MutationAssessor

Uncertain

2.4

M;M;.

MutationTaster

Benign

0.99

D;N

PrimateAI

Benign

0.48

PROVEAN

Pathogenic

-5.0

.;D;.

REVEL

Benign

0.24

Sift

Benign

0.030

.;D;.

Sift4G

Benign

0.070

.;T;T

Polyphen

1.0

D;D;.

Vest4

0.47, 0.46

MVP

0.84

MPC

0.40

ClinPred

0.65

GERP RS

0.048

Varity_R

0.48

gMVP

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0051

dbscSNV1_RF

Benign

0.12

SpliceAI score (max)

0.020

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