rs28371677

Positions:

• chr10-94942715-A-G

Variant summary

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

The ENST00000461906.1(CYP2C9):​c.*366A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 353,506 control chromosomes in the GnomAD database, including 7,096 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 0.21 (3595 hom., cov: 33)
  • Exomes 𝑓: 0.18 (3501 hom.)
• Consequence: CYP2C9 ENST00000461906.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.683

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2C9	NM_000771.4	c.481+374A>G		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+374A>G		intron_variant		1	NM_000771.4	ENSP00000260682.6

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32109 AN: 152036 Hom.: 3588 Cov.: 33

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.0896

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.216

GnomAD4 exome AF: 0.180 AC: 36176 AN: 201352 Hom.: 3501 Cov.: 0 AF XY: 0.176 AC XY: 19188 AN XY: 108740

Gnomad4 AFR exome AF: 0.285

Gnomad4 AMR exome AF: 0.140

Gnomad4 ASJ exome AF: 0.212

Gnomad4 EAS exome AF: 0.0983

Gnomad4 SAS exome AF: 0.160

Gnomad4 FIN exome AF: 0.184

Gnomad4 NFE exome AF: 0.188

Gnomad4 OTH exome AF: 0.181

GnomAD4 genome AF: 0.211 AC: 32143 AN: 152154 Hom.: 3595 Cov.: 33 AF XY: 0.209 AC XY: 15532 AN XY: 74378

Gnomad4 AFR AF: 0.279

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.224

Gnomad4 EAS AF: 0.0895

Gnomad4 SAS AF: 0.159

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.217

Alfa AF: 0.203 Hom.: 472

Bravo AF: 0.214

Asia WGS AF: 0.152 AC: 530 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.8
DANN	Benign	0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs28371677; hg19: chr10-96702472;