rs9325473

Variant names:

• chr10-94974825-G-A
• rs9325473
• NM_000771.4:c.961+2580G>A

Variant summary

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

The NM_000771.4(CYP2C9):​c.961+2580G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0494 in 152,084 control chromosomes in the GnomAD database, including 243 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 0.049 (243 hom., cov: 31)
• Consequence: CYP2C9 NM_000771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0760
• Publications: 4 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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C9	NM_000771.4	c.961+2580G>A		intron_variant	Intron 6 of 8	ENST00000260682.8	NP_000762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2C9	ENST00000260682.8	c.961+2580G>A		intron_variant	Intron 6 of 8	1	NM_000771.4	ENSP00000260682.6
CYP2C9	ENST00000643112.1	n.820-6358G>A		intron_variant	Intron 5 of 7			ENSP00000496202.1

Frequencies

GnomAD3 genomes AF: 0.0495 AC: 7526 AN: 151966 Hom.: 244 Cov.: 31

Gnomad AFR AF: 0.0126

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0494

Gnomad ASJ AF: 0.0825

Gnomad EAS AF: 0.0317

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0562

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0662

Gnomad OTH AF: 0.0526

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

GnomAD4 genome AF: 0.0494 AC: 7519 AN: 152084 Hom.: 243 Cov.: 31 AF XY: 0.0500 AC XY: 3720 AN XY: 74348

African (AFR) AF: 0.0126 AC: 522 AN: 41514

American (AMR) AF: 0.0492 AC: 751 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.0825 AC: 286 AN: 3466

East Asian (EAS) AF: 0.0318 AC: 164 AN: 5158

South Asian (SAS) AF: 0.114 AC: 548 AN: 4816

European-Finnish (FIN) AF: 0.0562 AC: 595 AN: 10592

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0662 AC: 4499 AN: 67966

Other (OTH) AF: 0.0511 AC: 108 AN: 2112

Alfa AF: 0.0630 Hom.: 434

Bravo AF: 0.0463

Asia WGS AF: 0.0770 AC: 267 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.0
DANN	Benign	0.50
PhyloP100		0.076
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: rs9325473; hg19: chr10-96734582;