10-95039038-C-T
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -5 ACMG points: 1P and 6B. PP3BP6_ModerateBS2
The NM_000770.3(CYP2C8):c.1150G>A(p.Gly384Ser) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00129 in 1,613,100 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00073 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0013 ( 8 hom. )
Consequence
CYP2C8
NM_000770.3 missense, splice_region
NM_000770.3 missense, splice_region
Scores
4
8
7
Splicing: ADA: 0.9918
2
Clinical Significance
Conservation
PhyloP100: 6.98
Publications
9 publications found
Genes affected
CYP2C8 (HGNC:2622): (cytochrome P450 family 2 subfamily C member 8) This gene 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 many xenobiotics, including the anticonvulsive drug mephenytoin, benzo(a)pyrene, 7-ethyoxycoumarin, and the anti-cancer drug taxol. This gene is located within a cluster of cytochrome P450 genes on chromosome 10q24. Several transcript variants encoding a few different isoforms have been found for this gene. [provided by RefSeq, Nov 2010]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -5 ACMG points.
PP3
Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.
BP6
Variant 10-95039038-C-T is Benign according to our data. Variant chr10-95039038-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 733649.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAdExome4 at 8 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CYP2C8 | NM_000770.3 | c.1150G>A | p.Gly384Ser | missense_variant, splice_region_variant | Exon 8 of 9 | ENST00000371270.6 | NP_000761.3 | |
CYP2C8 | NM_001198853.1 | c.940G>A | p.Gly314Ser | missense_variant, splice_region_variant | Exon 8 of 9 | NP_001185782.1 | ||
CYP2C8 | NM_001198855.1 | c.940G>A | p.Gly314Ser | missense_variant, splice_region_variant | Exon 9 of 10 | NP_001185784.1 | ||
CYP2C8 | NM_001198854.1 | c.844G>A | p.Gly282Ser | missense_variant, splice_region_variant | Exon 7 of 8 | NP_001185783.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000730 AC: 111AN: 152084Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
111
AN:
152084
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.000955 AC: 240AN: 251394 AF XY: 0.00114 show subpopulations
GnomAD2 exomes
AF:
AC:
240
AN:
251394
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00135 AC: 1970AN: 1460898Hom.: 8 Cov.: 30 AF XY: 0.00141 AC XY: 1027AN XY: 726848 show subpopulations
GnomAD4 exome
AF:
AC:
1970
AN:
1460898
Hom.:
Cov.:
30
AF XY:
AC XY:
1027
AN XY:
726848
show subpopulations
African (AFR)
AF:
AC:
11
AN:
33454
American (AMR)
AF:
AC:
37
AN:
44718
Ashkenazi Jewish (ASJ)
AF:
AC:
15
AN:
26126
East Asian (EAS)
AF:
AC:
1
AN:
39688
South Asian (SAS)
AF:
AC:
226
AN:
86240
European-Finnish (FIN)
AF:
AC:
1
AN:
53408
Middle Eastern (MID)
AF:
AC:
2
AN:
5766
European-Non Finnish (NFE)
AF:
AC:
1587
AN:
1111136
Other (OTH)
AF:
AC:
90
AN:
60362
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.460
Heterozygous variant carriers
0
97
193
290
386
483
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome AF: 0.000729 AC: 111AN: 152202Hom.: 0 Cov.: 32 AF XY: 0.000726 AC XY: 54AN XY: 74416 show subpopulations
GnomAD4 genome
AF:
AC:
111
AN:
152202
Hom.:
Cov.:
32
AF XY:
AC XY:
54
AN XY:
74416
show subpopulations
African (AFR)
AF:
AC:
12
AN:
41522
American (AMR)
AF:
AC:
9
AN:
15284
Ashkenazi Jewish (ASJ)
AF:
AC:
5
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5172
South Asian (SAS)
AF:
AC:
14
AN:
4824
European-Finnish (FIN)
AF:
AC:
0
AN:
10596
Middle Eastern (MID)
AF:
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
AC:
71
AN:
68016
Other (OTH)
AF:
AC:
0
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.499
Heterozygous variant carriers
0
6
12
19
25
31
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
6
ALSPAC
AF:
AC:
5
ESP6500AA
AF:
AC:
1
ESP6500EA
AF:
AC:
8
ExAC
AF:
AC:
95
Asia WGS
AF:
AC:
2
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Jul 17, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;.;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
.;.;.;H
PhyloP100
PrimateAI
Benign
T
PROVEAN
Pathogenic
.;D;.;D
REVEL
Pathogenic
Sift
Uncertain
.;D;.;D
Sift4G
Uncertain
D;D;D;D
Polyphen
0.98
.;.;.;D
Vest4
MVP
MPC
0.12
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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