rs2475376

Variant summary

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

The NM_000771.4(CYP2C9):​c.819+3359A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.838 in 152,140 control chromosomes in the GnomAD database, including 53,624 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.84 ( 53624 hom., cov: 32)

Consequence

CYP2C9
NM_000771.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.200
Variant links:
Genes affected
CYP2C9 (HGNC:2623): (cytochrome P450 family 2 subfamily C member 9) 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 rifampin. The enzyme is known to metabolize many xenobiotics, including phenytoin, tolbutamide, ibuprofen and S-warfarin. Studies identifying individuals who are poor metabolizers of phenytoin and tolbutamide suggest that this gene is polymorphic. The gene is located within a cluster of cytochrome P450 genes on chromosome 10q24. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-1.02).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CYP2C9NM_000771.4 linkuse as main transcriptc.819+3359A>G intron_variant ENST00000260682.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CYP2C9ENST00000260682.8 linkuse as main transcriptc.819+3359A>G intron_variant 1 NM_000771.4 P1P11712-1
CYP2C9ENST00000643112.1 linkuse as main transcriptc.819+3359A>G intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.837
AC:
127316
AN:
152022
Hom.:
53563
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.832
Gnomad AMI
AF:
0.891
Gnomad AMR
AF:
0.836
Gnomad ASJ
AF:
0.826
Gnomad EAS
AF:
0.622
Gnomad SAS
AF:
0.853
Gnomad FIN
AF:
0.905
Gnomad MID
AF:
0.778
Gnomad NFE
AF:
0.847
Gnomad OTH
AF:
0.814
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.838
AC:
127440
AN:
152140
Hom.:
53624
Cov.:
32
AF XY:
0.838
AC XY:
62348
AN XY:
74360
show subpopulations
Gnomad4 AFR
AF:
0.832
Gnomad4 AMR
AF:
0.836
Gnomad4 ASJ
AF:
0.826
Gnomad4 EAS
AF:
0.622
Gnomad4 SAS
AF:
0.853
Gnomad4 FIN
AF:
0.905
Gnomad4 NFE
AF:
0.847
Gnomad4 OTH
AF:
0.817
Alfa
AF:
0.843
Hom.:
69683
Bravo
AF:
0.828
Asia WGS
AF:
0.750
AC:
2602
AN:
3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
CADD
Benign
2.0
DANN
Benign
0.61

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: rs2475376; hg19: chr10-96712400; API