ENST00000461906.1:c.*231C>T

Variant names:

• chr10-94942580-C-T
• rs28371675
• ENST00000461906.1:c.*231C>T

Variant summary

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

The ENST00000461906.1(CYP2C9):​c.*231C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 638,216 control chromosomes in the GnomAD database, including 11,379 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 (1941 hom., cov: 33)
  • Exomes 𝑓: 0.19 (9438 hom.)
• Consequence: CYP2C9 ENST00000461906.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0400

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=-0.92).
• 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 rank	MANE	Protein	UniProt
CYP2C9	NM_000771.4	c.481+239C>T		intron_variant	Intron 3 of 8	ENST00000260682.8	NP_000762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2C9	ENST00000260682.8	c.481+239C>T		intron_variant	Intron 3 of 8	1	NM_000771.4	ENSP00000260682.6

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21257 AN: 152040 Hom.: 1938 Cov.: 33

Gnomad AFR AF: 0.0411

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.141

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: 0.186 AC: 90498 AN: 486058 Hom.: 9438 Cov.: 6 AF XY: 0.193 AC XY: 49050 AN XY: 254062

Gnomad4 AFR exome AF: 0.0405

Gnomad4 AMR exome AF: 0.115

Gnomad4 ASJ exome AF: 0.140

Gnomad4 EAS exome AF: 0.317

Gnomad4 SAS exome AF: 0.314

Gnomad4 FIN exome AF: 0.188

Gnomad4 NFE exome AF: 0.169

Gnomad4 OTH exome AF: 0.169

GnomAD4 genome AF: 0.140 AC: 21267 AN: 152158 Hom.: 1941 Cov.: 33 AF XY: 0.145 AC XY: 10765 AN XY: 74356

Gnomad4 AFR AF: 0.0410

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.307

Gnomad4 SAS AF: 0.318

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.133

Alfa AF: 0.150 Hom.: 299

Bravo AF: 0.127

Asia WGS AF: 0.294 AC: 1020 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.3
DANN	Benign	0.50

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: rs28371675; hg19: chr10-96702337;