rs4086116

Variant names:

• chr10-94947445-C-T
• rs4086116
• NM_000771.4:c.482-334C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000771.4(CYP2C9):​c.482-334C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,134 control chromosomes in the GnomAD database, including 2,880 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 0.19 (2880 hom., cov: 32)
• Consequence: CYP2C9 NM_000771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.199
• Publications: 50 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C9	NM_000771.4	c.482-334C>T		intron_variant	Intron 3 of 8	ENST00000260682.8	NP_000762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2C9	ENST00000260682.8	c.482-334C>T		intron_variant	Intron 3 of 8	1	NM_000771.4	ENSP00000260682.6
CYP2C9	ENST00000473496.1	n.253-334C>T		intron_variant	Intron 2 of 3	2
CYP2C9	ENST00000643112.1	n.482-334C>T		intron_variant	Intron 3 of 7			ENSP00000496202.1
CYP2C9	ENST00000645207.1	n.635-334C>T		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29006 AN: 152016 Hom.: 2878 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.0899

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.206

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.191 AC: 29030 AN: 152134 Hom.: 2880 Cov.: 32 AF XY: 0.188 AC XY: 14001 AN XY: 74386

African (AFR) AF: 0.214 AC: 8862 AN: 41506

American (AMR) AF: 0.164 AC: 2506 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 771 AN: 3470

East Asian (EAS) AF: 0.0897 AC: 464 AN: 5170

South Asian (SAS) AF: 0.159 AC: 767 AN: 4822

European-Finnish (FIN) AF: 0.174 AC: 1840 AN: 10598

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.194 AC: 13156 AN: 67986

Other (OTH) AF: 0.207 AC: 437 AN: 2112

Alfa AF: 0.194 Hom.: 12992

Bravo AF: 0.191

Asia WGS AF: 0.144 AC: 502 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.93
DANN	Benign	0.60
PhyloP100		-0.20
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

Other links and lift over

dbSNP: rs4086116; hg19: chr10-96707202;