rs2298037

Positions:

• chr10-94986321-C-T

Variant summary

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

The NM_000771.4(CYP2C9):​c.1291+147C>T 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 828,566 control chromosomes in the GnomAD database, including 14,225 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 (1923 hom., cov: 32)
  • Exomes 𝑓: 0.18 (12302 hom.)
• Consequence: CYP2C9 NM_000771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.876

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2C9	NM_000771.4	c.1291+147C>T		intron_variant		ENST00000260682.8	NP_000762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2C9	ENST00000260682.8	c.1291+147C>T		intron_variant		1	NM_000771.4	ENSP00000260682.6
CYP2C9	ENST00000643112.1	n.*300+147C>T		intron_variant				ENSP00000496202.1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 21040 AN: 152042 Hom.: 1920 Cov.: 32

Gnomad AFR AF: 0.0368

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.128

GnomAD4 exome AF: 0.177 AC: 119852 AN: 676406 Hom.: 12302 AF XY: 0.184 AC XY: 65519 AN XY: 355910

Gnomad4 AFR exome AF: 0.0355

Gnomad4 AMR exome AF: 0.108

Gnomad4 ASJ exome AF: 0.138

Gnomad4 EAS exome AF: 0.313

Gnomad4 SAS exome AF: 0.307

Gnomad4 FIN exome AF: 0.181

Gnomad4 NFE exome AF: 0.163

Gnomad4 OTH exome AF: 0.163

GnomAD4 genome AF: 0.138 AC: 21047 AN: 152160 Hom.: 1923 Cov.: 32 AF XY: 0.143 AC XY: 10653 AN XY: 74376

Gnomad4 AFR AF: 0.0367

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.307

Gnomad4 SAS AF: 0.318

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.132

Alfa AF: 0.160 Hom.: 2060

Bravo AF: 0.125

Asia WGS AF: 0.293 AC: 1017 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.090
DANN	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs2298037; hg19: chr10-96746078;