Variant rs28399499 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000767.5(CYP2B6):c.983T>C(p.Ile328Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0203 in 152082 control chromosomes in the gnomAD Genomes database, including 110 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as drug response (★★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.020 ( 110 hom., cov: 32)

Exomes 𝑓: 0.0051 ( 54 hom. )

Consequence

CYP2B6
NM_000767.5 missense

Scores

Clinical Significance

drug response reviewed by expert panel O:1

Conservation

PhyloP100: 7.60

Links

CYP2B6 (HGNC:2615):

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0061822236).

BA1

GnomAd highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2B6	NM_000767.5 linkuse as main transcript	c.983T>C	p.Ile328Thr	missense_variant	7/9	ENST00000324071.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2B6	ENST00000324071.10 linkuse as main transcript	c.983T>C	p.Ile328Thr	missense_variant	7/9	1	NM_000767.5	P1	P20813-1
CYP2B6	ENST00000597612.1 linkuse as main transcript	n.478T>C		non_coding_transcript_exon_variant	2/3	1
CYP2B6	ENST00000593831.1 linkuse as main transcript	c.275T>C	p.Ile92Thr	missense_variant	3/5	2
CYP2B6	ENST00000598834.2 linkuse as main transcript	c.*424T>C		3_prime_UTR_variant, NMD_transcript_variant	8/10	5

Frequencies

GnomAD3 genomes

AF:

0.0203

AC:

3085

AN:

152082

Hom.:

110

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0704

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00859

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.00508

AC:

1277

AN:

251302

Hom.:

AF XY:

0.00355

AC XY:

482

AN XY:

135840

show subpopulations

Gnomad AFR exome

AF:

0.0694

Gnomad AMR exome

AF:

0.00341

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000150

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00191

AC:

2791

AN:

1461858

Hom.:

AF XY:

0.00165

AC XY:

1202

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.0681

Gnomad4 AMR exome

AF:

0.00356

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000791

Gnomad4 OTH exome

AF:

0.00391

Alfa

AF:

0.00420

Hom.:

Bravo

AF:

0.0229

ESP6500AA

AF:

0.0622

AC:

274

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.00646

AC:

784

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000178

ClinVar

Significance: drug response

Submissions summary: Other:1

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

nevirapine response - Toxicity

Other:1

drug response, reviewed by expert panel

curation

PharmGKB

Mar 24, 2021

PharmGKB Level of Evidence 2A: Variants in Level 2A clinical annotations are found in PharmGKB’s Tier 1 Very Important Pharmacogenes (VIPs). These variants are in known pharmacogenes, implying causation of drug phenotype is more likely. These clinical annotations describe variant-drug combinations with a moderate level of evidence supporting the association. For example, the association may be found in multiple cohorts, but there may be a minority of studies that do not support the majority assertion. Level 2A clinical annotations must be supported by at least two independent publications. Drug-variant association: Toxicity

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.16

Cadd

Pathogenic

Dann

Uncertain

0.98

DEOGEN2

Benign

0.092

T;T;T

Eigen

Pathogenic

0.73

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Pathogenic

0.99

MetaRNN

Benign

0.0062

T;T;T

MetaSVM

Benign

-0.31

MutationAssessor

Pathogenic

3.9

H;H;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.68

Polyphen

0.99

D;D;.

Vest4

0.81, 0.86

MVP

0.92

MPC

0.45

ClinPred

0.084

GERP RS

4.3

Varity_R

0.92

gMVP

0.41

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

Links

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over