rs9332197

Variant names:

• chr10-94981151-T-C
• rs9332197
• NM_000771.4:c.962-32T>C

Variant summary

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

The NM_000771.4(CYP2C9):​c.962-32T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0525 in 1,612,114 control chromosomes in the GnomAD database, including 2,506 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 0.039 (144 hom., cov: 32)
  • Exomes 𝑓: 0.054 (2362 hom.)
• Consequence: CYP2C9 NM_000771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210
• Publications: 9 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C9	NM_000771.4	c.962-32T>C		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.962-32T>C		intron_variant	Intron 6 of 8	1	NM_000771.4	ENSP00000260682.6
CYP2C9	ENST00000643112.1	n.820-32T>C		intron_variant	Intron 5 of 7			ENSP00000496202.1

Frequencies

GnomAD3 genomes AF: 0.0394 AC: 5994 AN: 152116 Hom.: 144 Cov.: 32

Gnomad AFR AF: 0.0102

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0300

Gnomad ASJ AF: 0.0424

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0435

Gnomad FIN AF: 0.0782

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0561

Gnomad OTH AF: 0.0345

GnomAD2 exomes AF: 0.0460 AC: 11527 AN: 250424 AF XY: 0.0475

Gnomad AFR exome AF: 0.00861

Gnomad AMR exome AF: 0.0229

Gnomad ASJ exome AF: 0.0406

Gnomad EAS exome AF: 0.000272

Gnomad FIN exome AF: 0.0822

Gnomad NFE exome AF: 0.0587

Gnomad OTH exome AF: 0.0492

GnomAD4 exome AF: 0.0539 AC: 78672 AN: 1459880 Hom.: 2362 Cov.: 31 AF XY: 0.0537 AC XY: 38981 AN XY: 726330

African (AFR) AF: 0.00805 AC: 269 AN: 33430

American (AMR) AF: 0.0233 AC: 1042 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.0384 AC: 1003 AN: 26108

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39688

South Asian (SAS) AF: 0.0499 AC: 4298 AN: 86214

European-Finnish (FIN) AF: 0.0807 AC: 4308 AN: 53386

Middle Eastern (MID) AF: 0.0243 AC: 140 AN: 5762

European-Non Finnish (NFE) AF: 0.0582 AC: 64656 AN: 1110356

Other (OTH) AF: 0.0490 AC: 2954 AN: 60300

GnomAD4 genome AF: 0.0394 AC: 5992 AN: 152234 Hom.: 144 Cov.: 32 AF XY: 0.0402 AC XY: 2992 AN XY: 74432

African (AFR) AF: 0.0102 AC: 424 AN: 41564

American (AMR) AF: 0.0299 AC: 457 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0424 AC: 147 AN: 3468

East Asian (EAS) AF: 0.000966 AC: 5 AN: 5178

South Asian (SAS) AF: 0.0434 AC: 209 AN: 4820

European-Finnish (FIN) AF: 0.0782 AC: 829 AN: 10602

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0561 AC: 3813 AN: 67998

Other (OTH) AF: 0.0342 AC: 72 AN: 2106

Alfa AF: 0.0487 Hom.: 345

Bravo AF: 0.0349

Asia WGS AF: 0.0210 AC: 74 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.0
DANN	Benign	0.65
PhyloP100		-0.021
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: rs9332197; hg19: chr10-96740908;