rs9332129

Positions:

• chr10-94948993-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.643-115A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0211 in 531,770 control chromosomes in the GnomAD database, including 735 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 0.044 (456 hom., cov: 32)
  • Exomes 𝑓: 0.012 (279 hom.)
• Consequence: CYP2C9 NM_000771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.131

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=-0.91).
• 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.643-115A>G		intron_variant		ENST00000260682.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2C9	ENST00000260682.8	c.643-115A>G		intron_variant		1	NM_000771.4	P1
CYP2C9	ENST00000643112.1	c.643-115A>G		intron_variant, NMD_transcript_variant
CYP2C9	ENST00000473496.1	n.414-115A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0436 AC: 6620 AN: 151974 Hom.: 453 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0147

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0571

Gnomad SAS AF: 0.00518

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000515

Gnomad OTH AF: 0.0306

GnomAD4 exome AF: 0.0121 AC: 4585 AN: 379676 Hom.: 279 AF XY: 0.0110 AC XY: 2189 AN XY: 199782

Gnomad4 AFR exome AF: 0.158

Gnomad4 AMR exome AF: 0.00992

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0990

Gnomad4 SAS exome AF: 0.00367

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000469

Gnomad4 OTH exome AF: 0.0155

GnomAD4 genome AF: 0.0436 AC: 6638 AN: 152094 Hom.: 456 Cov.: 32 AF XY: 0.0419 AC XY: 3117 AN XY: 74348

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.0147

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0570

Gnomad4 SAS AF: 0.00518

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000515

Gnomad4 OTH AF: 0.0345

Alfa AF: 0.0279 Hom.: 36

Bravo AF: 0.0492

Asia WGS AF: 0.0480 AC: 166 AN: 3446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9332129; hg19: chr10-96708750;