rs9332121

chr10-94942182-T-A

Variant summary

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

The NM_000771.4(CYP2C9):c.332-10T>A variant causes a splice polypyrimidine tract, 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.041 (445 hom., cov: 32)
  • Exomes 𝑓: 0.0043 (450 hom.)
• Consequence: CYP2C9 NM_000771.4 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0001219
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2C9	NM_000771.4	c.332-10T>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000260682.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2C9	ENST00000260682.8	c.332-10T>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000771.4	P1

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

GnomAD3 exomes AF: 0.0107 AC: 2686 AN: 251142 Hom.: 217 AF XY: 0.00792 AC XY: 1075 AN XY: 135714

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 SAS exome AF: 0.000261

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

Gnomad4 AFR exome AF: 0.155

Gnomad4 AMR exome AF: 0.00696

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000301

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000116

Gnomad4 OTH exome AF: 0.00881

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

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.0143

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000623

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000338

Gnomad4 OTH AF: 0.0284

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	18
Dann	Benign	0.29

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

Publications

LitVar

Other links and lift over

dbSNP: rs9332121; hg19: chr10-96701939;