10-94942093-T-C

Variant names:

• chr10-94942093-T-C
• rs9332120
• NM_000771.4:c.331+73T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000771.4(CYP2C9):​c.331+73T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 1,612,374 control chromosomes in the GnomAD database, including 33,260 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 0.19 (2966 hom., cov: 32)
  • Exomes 𝑓: 0.20 (30294 hom.)
• Consequence: CYP2C9 NM_000771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.53
• Publications: 10 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000771.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2C9	NM_000771.4	MANE Select	c.331+73T>C		intron	N/A	NP_000762.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2C9	ENST00000260682.8	TSL:1 MANE Select	c.331+73T>C		intron	N/A	ENSP00000260682.6
	CYP2C9	ENST00000461906.1	TSL:1	c.331+73T>C		intron	N/A	ENSP00000495649.1
	CYP2C9	ENST00000473496.1	TSL:2	n.102+73T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29025 AN: 152048 Hom.: 2965 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.00944

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.191

GnomAD4 exome AF: 0.199 AC: 290478 AN: 1460208 Hom.: 30294 Cov.: 35 AF XY: 0.199 AC XY: 144805 AN XY: 726384

African (AFR) AF: 0.193 AC: 6448 AN: 33424

American (AMR) AF: 0.102 AC: 4548 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 5603 AN: 26126

East Asian (EAS) AF: 0.00883 AC: 350 AN: 39618

South Asian (SAS) AF: 0.169 AC: 14608 AN: 86204

European-Finnish (FIN) AF: 0.189 AC: 10097 AN: 53396

Middle Eastern (MID) AF: 0.209 AC: 998 AN: 4768

European-Non Finnish (NFE) AF: 0.213 AC: 236347 AN: 1111754

Other (OTH) AF: 0.191 AC: 11479 AN: 60254

GnomAD4 genome AF: 0.191 AC: 29022 AN: 152166 Hom.: 2966 Cov.: 32 AF XY: 0.188 AC XY: 13976 AN XY: 74400

African (AFR) AF: 0.195 AC: 8087 AN: 41504

American (AMR) AF: 0.129 AC: 1968 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 738 AN: 3468

East Asian (EAS) AF: 0.00947 AC: 49 AN: 5176

South Asian (SAS) AF: 0.163 AC: 789 AN: 4832

European-Finnish (FIN) AF: 0.182 AC: 1925 AN: 10590

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14759 AN: 67992

Other (OTH) AF: 0.188 AC: 398 AN: 2114

Alfa AF: 0.204 Hom.: 5254

Bravo AF: 0.186

Asia WGS AF: 0.0830 AC: 290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.55
DANN	Benign	0.39
PhyloP100		-3.5
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: rs9332120; hg19: chr10-96701850; COSMIC: COSV53248838; COSMIC: COSV53248838;