10-94942715-A-G

Variant names:

• chr10-94942715-A-G
• rs28371677
• ENST00000461906.1:c.*366A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.275 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+374A>G		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.*366A>G		3_prime_UTR	Exon 3 of 3	ENSP00000495649.1	P11712-2
	CYP2C9	ENST00000260682.8	TSL:1 MANE Select	c.481+374A>G		intron	N/A	ENSP00000260682.6	P11712-1
	CYP2C9	ENST00000880948.1		c.481+374A>G		intron	N/A	ENSP00000551007.1

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

African (AFR) AF: 0.285 AC: 1692 AN: 5946

American (AMR) AF: 0.140 AC: 1377 AN: 9856

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 1087 AN: 5120

East Asian (EAS) AF: 0.0983 AC: 883 AN: 8986

South Asian (SAS) AF: 0.160 AC: 5758 AN: 36094

European-Finnish (FIN) AF: 0.184 AC: 1619 AN: 8794

Middle Eastern (MID) AF: 0.223 AC: 171 AN: 768

European-Non Finnish (NFE) AF: 0.188 AC: 21744 AN: 115582

Other (OTH) AF: 0.181 AC: 1845 AN: 10206

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

African (AFR) AF: 0.279 AC: 11572 AN: 41482

American (AMR) AF: 0.170 AC: 2606 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 776 AN: 3472

East Asian (EAS) AF: 0.0895 AC: 463 AN: 5176

South Asian (SAS) AF: 0.159 AC: 768 AN: 4824

European-Finnish (FIN) AF: 0.189 AC: 2004 AN: 10590

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13269 AN: 68000

Other (OTH) AF: 0.217 AC: 458 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.8
DANN	Benign	0.36
PhyloP100		-0.68
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs28371677; hg19: chr10-96702472;