10-95037713-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000770.3(CYP2C8):​c.1292-404G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.687 in 152,040 control chromosomes in the GnomAD database, including 36,575 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

Frequency

Genomes: 𝑓 0.69 ( 36575 hom., cov: 32)

Consequence

CYP2C8
NM_000770.3 intron

Scores

2

Clinical Significance

association no assertion criteria provided O:1

Conservation

PhyloP100: -1.88

Publications

14 publications found
Variant links:
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]

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-1.01).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CYP2C8NM_000770.3 linkc.1292-404G>A intron_variant Intron 8 of 8 ENST00000371270.6 NP_000761.3 P10632-1
CYP2C8NM_001198853.1 linkc.1082-404G>A intron_variant Intron 8 of 8 NP_001185782.1 P10632B7Z1F5
CYP2C8NM_001198855.1 linkc.1082-404G>A intron_variant Intron 9 of 9 NP_001185784.1 P10632B7Z1F5
CYP2C8NM_001198854.1 linkc.986-404G>A intron_variant Intron 7 of 7 NP_001185783.1 P10632-2B7Z1F5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CYP2C8ENST00000371270.6 linkc.1292-404G>A intron_variant Intron 8 of 8 1 NM_000770.3 ENSP00000360317.3 P10632-1

Frequencies

GnomAD3 genomes
AF:
0.687
AC:
104304
AN:
151922
Hom.:
36523
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.807
Gnomad AMI
AF:
0.738
Gnomad AMR
AF:
0.558
Gnomad ASJ
AF:
0.706
Gnomad EAS
AF:
0.461
Gnomad SAS
AF:
0.668
Gnomad FIN
AF:
0.616
Gnomad MID
AF:
0.835
Gnomad NFE
AF:
0.669
Gnomad OTH
AF:
0.704
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.687
AC:
104405
AN:
152040
Hom.:
36575
Cov.:
32
AF XY:
0.681
AC XY:
50604
AN XY:
74318
show subpopulations
African (AFR)
AF:
0.807
AC:
33473
AN:
41478
American (AMR)
AF:
0.557
AC:
8508
AN:
15276
Ashkenazi Jewish (ASJ)
AF:
0.706
AC:
2450
AN:
3468
East Asian (EAS)
AF:
0.461
AC:
2385
AN:
5172
South Asian (SAS)
AF:
0.669
AC:
3225
AN:
4818
European-Finnish (FIN)
AF:
0.616
AC:
6495
AN:
10548
Middle Eastern (MID)
AF:
0.840
AC:
247
AN:
294
European-Non Finnish (NFE)
AF:
0.669
AC:
45458
AN:
67962
Other (OTH)
AF:
0.706
AC:
1491
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
1641
3281
4922
6562
8203
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
818
1636
2454
3272
4090
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.673
Hom.:
108031
Bravo
AF:
0.684
Asia WGS
AF:
0.607
AC:
2109
AN:
3478

ClinVar

Significance: association
Submissions summary: Other:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Pulmonary disease, chronic obstructive, susceptibility to Other:1
Jul 05, 2022
HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas
Significance:association
Review Status:no assertion criteria provided
Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
CADD
Benign
0.13
DANN
Benign
0.20
PhyloP100
-1.9
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs1934953; hg19: chr10-96797470; API