10-94942093-T-C

Position:

• chr10-94942093-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 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. Variant has been reported in Lovd as Likely benign (no stars).

• 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

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 10-94942093-T-C is Benign according to our data. Variant chr10-94942093-T-C is described in Lovd as [Likely_benign].
• 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.331+73T>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.331+73T>C		intron_variant		1	NM_000771.4	ENSP00000260682	P1

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

Gnomad4 AFR exome AF: 0.193

Gnomad4 AMR exome AF: 0.102

Gnomad4 ASJ exome AF: 0.214

Gnomad4 EAS exome AF: 0.00883

Gnomad4 SAS exome AF: 0.169

Gnomad4 FIN exome AF: 0.189

Gnomad4 NFE exome AF: 0.213

Gnomad4 OTH exome AF: 0.191

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

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.00947

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.188

Alfa AF: 0.206 Hom.: 433

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	-0.88
CADD	Benign	0.55
DANN	Benign	0.39

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: rs9332120; hg19: chr10-96701850; COSMIC: COSV53248838; COSMIC: COSV53248838;