10-94938933-T-C

Position:

• chr10-94938933-T-C

Variant summary

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

The NM_000771.4(CYP2C9):​c.168+83T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 1,439,892 control chromosomes in the GnomAD database, including 29,433 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 (2965 hom., cov: 32)
  • Exomes 𝑓: 0.20 (26468 hom.)
• Consequence: CYP2C9 NM_000771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.48

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=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2C9	NM_000771.4	c.168+83T>C		intron_variant		ENST00000260682.8	NP_000762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2C9	ENST00000260682.8	c.168+83T>C		intron_variant		1	NM_000771.4	ENSP00000260682.6
CYP2C9	ENST00000461906.1	c.168+83T>C		intron_variant		1		ENSP00000495649.1
CYP2C9	ENST00000643112.1	n.168+83T>C		intron_variant				ENSP00000496202.1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29024 AN: 152078 Hom.: 2964 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.00942

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.191

GnomAD4 exome AF: 0.197 AC: 253661 AN: 1287696 Hom.: 26468 AF XY: 0.198 AC XY: 128470 AN XY: 649954

Gnomad4 AFR exome AF: 0.193

Gnomad4 AMR exome AF: 0.102

Gnomad4 ASJ exome AF: 0.215

Gnomad4 EAS exome AF: 0.00889

Gnomad4 SAS exome AF: 0.170

Gnomad4 FIN exome AF: 0.189

Gnomad4 NFE exome AF: 0.212

Gnomad4 OTH exome AF: 0.190

GnomAD4 genome AF: 0.191 AC: 29021 AN: 152196 Hom.: 2965 Cov.: 32 AF XY: 0.188 AC XY: 13974 AN XY: 74404

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.212

Gnomad4 EAS AF: 0.00944

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.189

Alfa AF: 0.202 Hom.: 3243

Bravo AF: 0.186

Asia WGS AF: 0.0830 AC: 290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.41
DANN	Benign	0.52

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: rs9332104; hg19: chr10-96698690; COSMIC: COSV53252617; COSMIC: COSV53252617;