rs9332172

Positions:

• chr10-94972031-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000771.4(CYP2C9):​c.820-73A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 1,547,338 control chromosomes in the GnomAD database, including 30,553 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 0.21 (3584 hom., cov: 32)
  • Exomes 𝑓: 0.19 (26969 hom.)
• Consequence: CYP2C9 NM_000771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2C9	NM_000771.4	c.820-73A>G		intron_variant		ENST00000260682.8	NP_000762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2C9	ENST00000260682.8	c.820-73A>G		intron_variant		1	NM_000771.4	ENSP00000260682	P1
CYP2C9	ENST00000643112.1	c.820-9152A>G		intron_variant, NMD_transcript_variant				ENSP00000496202

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32083 AN: 151950 Hom.: 3577 Cov.: 32

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.0893

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.215

GnomAD4 exome AF: 0.193 AC: 269688 AN: 1395270 Hom.: 26969 AF XY: 0.192 AC XY: 134193 AN XY: 698250

Gnomad4 AFR exome AF: 0.296

Gnomad4 AMR exome AF: 0.123

Gnomad4 ASJ exome AF: 0.227

Gnomad4 EAS exome AF: 0.117

Gnomad4 SAS exome AF: 0.163

Gnomad4 FIN exome AF: 0.188

Gnomad4 NFE exome AF: 0.198

Gnomad4 OTH exome AF: 0.192

GnomAD4 genome AF: 0.211 AC: 32117 AN: 152068 Hom.: 3584 Cov.: 32 AF XY: 0.209 AC XY: 15507 AN XY: 74346

Gnomad4 AFR AF: 0.279

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.223

Gnomad4 EAS AF: 0.0891

Gnomad4 SAS AF: 0.159

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.216

Alfa AF: 0.207 Hom.: 3355

Bravo AF: 0.214

Asia WGS AF: 0.152 AC: 528 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.19
DANN	Benign	0.69

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

Other links and lift over

dbSNP: rs9332172; hg19: chr10-96731788;