rs9332121

Variant names:

• chr10-94942182-T-A
• rs9332121
• NM_000771.4:c.332-10T>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.332-10T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00775 in 1,613,566 control chromosomes in the GnomAD database, including 895 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.041 (445 hom., cov: 32)
  • Exomes 𝑓: 0.0043 (450 hom.)
• Consequence: CYP2C9 NM_000771.4 intron
• Scores: Splicing: ADA: 0.0001219
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40
• Publications: 8 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000771.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2C9	NM_000771.4	MANE Select	c.332-10T>A		intron	N/A	NP_000762.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2C9	ENST00000260682.8	TSL:1 MANE Select	c.332-10T>A		intron	N/A	ENSP00000260682.6
	CYP2C9	ENST00000461906.1	TSL:1	c.332-10T>A		intron	N/A	ENSP00000495649.1
	CYP2C9	ENST00000880956.1		c.343T>A	p.Phe115Ile	missense	Exon 3 of 9	ENSP00000551015.1

Frequencies

GnomAD3 genomes AF: 0.0412 AC: 6263 AN: 152126 Hom.: 444 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0143

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.0287

GnomAD2 exomes AF: 0.0107 AC: 2686 AN: 251142 AF XY: 0.00792

Gnomad AFR exome AF: 0.148

Gnomad AMR exome AF: 0.00600

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000229

Gnomad OTH exome AF: 0.00539

GnomAD4 exome AF: 0.00426 AC: 6229 AN: 1461322 Hom.: 450 Cov.: 33 AF XY: 0.00365 AC XY: 2652 AN XY: 726964

African (AFR) AF: 0.155 AC: 5190 AN: 33450

American (AMR) AF: 0.00696 AC: 311 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39646

South Asian (SAS) AF: 0.000301 AC: 26 AN: 86250

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53412

Middle Eastern (MID) AF: 0.00724 AC: 40 AN: 5526

European-Non Finnish (NFE) AF: 0.000116 AC: 129 AN: 1111876

Other (OTH) AF: 0.00881 AC: 532 AN: 60358

GnomAD4 genome AF: 0.0412 AC: 6272 AN: 152244 Hom.: 445 Cov.: 32 AF XY: 0.0393 AC XY: 2924 AN XY: 74448

African (AFR) AF: 0.144 AC: 5968 AN: 41528

American (AMR) AF: 0.0143 AC: 218 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000338 AC: 23 AN: 68020

Other (OTH) AF: 0.0284 AC: 60 AN: 2112

Alfa AF: 0.0236 Hom.: 42

Bravo AF: 0.0468

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	18
DANN	Benign	0.29
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00012
dbscSNV1_RF	Benign	0.048
SpliceAI score (max)		0.50		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.50		Position offset: 23

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9332121; hg19: chr10-96701939;