rs9332238

Variant names:

• chr10-94988735-G-A
• rs9332238
• NM_000771.4:c.1292-112G>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.1292-112G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 1,141,504 control chromosomes in the GnomAD database, including 18,541 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 0.14 (1845 hom., cov: 32)
  • Exomes 𝑓: 0.18 (16696 hom.)
• Consequence: CYP2C9 NM_000771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• Publications: 13 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C9	NM_000771.4	c.1292-112G>A		intron_variant	Intron 8 of 8	ENST00000260682.8	NP_000762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2C9	ENST00000260682.8	c.1292-112G>A		intron_variant	Intron 8 of 8	1	NM_000771.4	ENSP00000260682.6
CYP2C9	ENST00000643112.1	n.*301-112G>A		intron_variant	Intron 7 of 7			ENSP00000496202.1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20907 AN: 151806 Hom.: 1845 Cov.: 32

Gnomad AFR AF: 0.0361

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.0328

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.205

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.166

GnomAD4 exome AF: 0.175 AC: 173565 AN: 989578 Hom.: 16696 AF XY: 0.176 AC XY: 90163 AN XY: 512588

African (AFR) AF: 0.0334 AC: 809 AN: 24212

American (AMR) AF: 0.111 AC: 4807 AN: 43174

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 4957 AN: 22660

East Asian (EAS) AF: 0.0300 AC: 1120 AN: 37304

South Asian (SAS) AF: 0.158 AC: 11854 AN: 75178

European-Finnish (FIN) AF: 0.176 AC: 9150 AN: 51972

Middle Eastern (MID) AF: 0.194 AC: 626 AN: 3224

European-Non Finnish (NFE) AF: 0.193 AC: 132800 AN: 687420

Other (OTH) AF: 0.167 AC: 7442 AN: 44434

GnomAD4 genome AF: 0.138 AC: 20897 AN: 151926 Hom.: 1845 Cov.: 32 AF XY: 0.137 AC XY: 10170 AN XY: 74254

African (AFR) AF: 0.0360 AC: 1493 AN: 41446

American (AMR) AF: 0.147 AC: 2238 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 754 AN: 3466

East Asian (EAS) AF: 0.0327 AC: 169 AN: 5170

South Asian (SAS) AF: 0.154 AC: 741 AN: 4812

European-Finnish (FIN) AF: 0.174 AC: 1828 AN: 10526

Middle Eastern (MID) AF: 0.205 AC: 60 AN: 292

European-Non Finnish (NFE) AF: 0.193 AC: 13104 AN: 67928

Other (OTH) AF: 0.163 AC: 344 AN: 2112

Alfa AF: 0.175 Hom.: 5824

Bravo AF: 0.132

Asia WGS AF: 0.0930 AC: 326 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.71
DANN	Benign	0.38
PhyloP100		-1.5
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: rs9332238; hg19: chr10-96748492;