rs28371675

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000461906.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2C9	NM_000771.4	MANE Select	c.481+239C>T		intron	N/A	NP_000762.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2C9	ENST00000461906.1	TSL:1	c.*231C>T		3_prime_UTR	Exon 3 of 3	ENSP00000495649.1	P11712-2
	CYP2C9	ENST00000260682.8	TSL:1 MANE Select	c.481+239C>T		intron	N/A	ENSP00000260682.6	P11712-1
	CYP2C9	ENST00000880948.1		c.481+239C>T		intron	N/A	ENSP00000551007.1

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

African (AFR) AF: 0.0405 AC: 525 AN: 12954

American (AMR) AF: 0.115 AC: 2130 AN: 18554

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 1933 AN: 13812

East Asian (EAS) AF: 0.317 AC: 9571 AN: 30230

South Asian (SAS) AF: 0.314 AC: 14136 AN: 44996

European-Finnish (FIN) AF: 0.188 AC: 5915 AN: 31464

Middle Eastern (MID) AF: 0.110 AC: 220 AN: 2004

European-Non Finnish (NFE) AF: 0.169 AC: 51535 AN: 305200

Other (OTH) AF: 0.169 AC: 4533 AN: 26844

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

African (AFR) AF: 0.0410 AC: 1705 AN: 41538

American (AMR) AF: 0.127 AC: 1942 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 488 AN: 3470

East Asian (EAS) AF: 0.307 AC: 1586 AN: 5160

South Asian (SAS) AF: 0.318 AC: 1534 AN: 4820

European-Finnish (FIN) AF: 0.194 AC: 2056 AN: 10582

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11466 AN: 67986

Other (OTH) AF: 0.133 AC: 280 AN: 2110

Alfa AF: 0.152 Hom.: 710

Bravo AF: 0.127

Asia WGS AF: 0.294 AC: 1020 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.3
DANN	Benign	0.50
PhyloP100		-0.040
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs28371675; hg19: chr10-96702337;