rs2860905

Positions:

• chr10-94942538-G-A

Variant summary

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

The ENST00000461906.1(CYP2C9):​c.*189G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 825,570 control chromosomes in the GnomAD database, including 19,597 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 0.24 (4413 hom., cov: 32)
  • Exomes 𝑓: 0.21 (15184 hom.)
• Consequence: CYP2C9 ENST00000461906.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2C9	NM_000771.4	c.481+197G>A		intron_variant		ENST00000260682.8	NP_000762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2C9	ENST00000260682.8	c.481+197G>A		intron_variant		1	NM_000771.4	ENSP00000260682	P1

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35869 AN: 151998 Hom.: 4407 Cov.: 32

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.0938

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.256

GnomAD4 exome AF: 0.208 AC: 139999 AN: 673454 Hom.: 15184 Cov.: 9 AF XY: 0.207 AC XY: 72626 AN XY: 350486

Gnomad4 AFR exome AF: 0.284

Gnomad4 AMR exome AF: 0.150

Gnomad4 ASJ exome AF: 0.288

Gnomad4 EAS exome AF: 0.122

Gnomad4 SAS exome AF: 0.190

Gnomad4 FIN exome AF: 0.207

Gnomad4 NFE exome AF: 0.213

Gnomad4 OTH exome AF: 0.217

GnomAD4 genome AF: 0.236 AC: 35899 AN: 152116 Hom.: 4413 Cov.: 32 AF XY: 0.232 AC XY: 17255 AN XY: 74372

Gnomad4 AFR AF: 0.286

Gnomad4 AMR AF: 0.200

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.0936

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.206

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.256

Alfa AF: 0.231 Hom.: 710

Bravo AF: 0.239

Asia WGS AF: 0.167 AC: 580 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.97
DANN	Benign	0.55

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: rs2860905; hg19: chr10-96702295; COSMIC: COSV53248739; COSMIC: COSV53248739;