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GeneBe

rs28399499

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

3
4
6

Clinical Significance

drug response reviewed by expert panel O:1

Conservation

PhyloP100: 7.60

Links

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
CYP2B6NM_000767.5 linkuse as main transcriptc.983T>C p.Ile328Thr missense_variant 7/9 ENST00000324071.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CYP2B6ENST00000324071.10 linkuse as main transcriptc.983T>C p.Ile328Thr missense_variant 7/91 NM_000767.5 P1P20813-1
CYP2B6ENST00000597612.1 linkuse as main transcriptn.478T>C non_coding_transcript_exon_variant 2/31
CYP2B6ENST00000593831.1 linkuse as main transcriptc.275T>C p.Ile92Thr missense_variant 3/52
CYP2B6ENST00000598834.2 linkuse as main transcriptc.*424T>C 3_prime_UTR_variant, NMD_transcript_variant 8/105

Frequencies

GnomAD3 genomes
AF:
0.0203
AC:
3085
AN:
152082
Hom.:
110
Cov.:
32
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.:
54
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.:
85
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.:
46
Bravo
AF:
0.0229
ESP6500AA
AF:
0.0622
AC:
274
ESP6500EA
AF:
0.000581
AC:
5
ExAC
AF:
0.00646
AC:
784
Asia WGS
AF:
0.00375
AC:
13
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 panelcurationPharmGKBMar 24, 2021PharmGKB 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
T
BayesDel_noAF
Benign
-0.16
Cadd
Pathogenic
27
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
D
MetaRNN
Benign
0.0062
T;T;T
MetaSVM
Benign
-0.31
T
MutationAssessor
Pathogenic
3.9
H;H;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.68
T
Polyphen
0.99
D;D;.
Vest4
0.81, 0.86
MVP
0.92
MPC
0.45
ClinPred
0.084
T
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.

Other links and lift over

dbSNP: rs28399499; hg19: chr19-41518221; COSMIC: COSV57844857;