10-94947714-G-C

Position:

• chr10-94947714-G-C

Variant summary

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

The ENST00000260682.8(CYP2C9):​c.482-65G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0105 in 1,581,852 control chromosomes in the GnomAD database, including 1,061 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 0.044 (459 hom., cov: 32)
  • Exomes 𝑓: 0.0069 (602 hom.)
• Consequence: CYP2C9 ENST00000260682.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2C9	NM_000771.4	c.482-65G>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.482-65G>C		intron_variant		1	NM_000771.4	ENSP00000260682	P1
CYP2C9	ENST00000643112.1	c.482-65G>C		intron_variant, NMD_transcript_variant				ENSP00000496202
CYP2C9	ENST00000473496.1	n.253-65G>C		intron_variant, non_coding_transcript_variant		2
CYP2C9	ENST00000645207.1	n.635-65G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0436 AC: 6634 AN: 152022 Hom.: 456 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0149

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0572

Gnomad SAS AF: 0.00518

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000515

Gnomad OTH AF: 0.0306

GnomAD4 exome AF: 0.00692 AC: 9889 AN: 1429712 Hom.: 602 AF XY: 0.00638 AC XY: 4542 AN XY: 712028

Gnomad4 AFR exome AF: 0.155

Gnomad4 AMR exome AF: 0.00712

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0871

Gnomad4 SAS exome AF: 0.00359

Gnomad4 FIN exome AF: 0.0000189

Gnomad4 NFE exome AF: 0.000217

Gnomad4 OTH exome AF: 0.0126

GnomAD4 genome AF: 0.0437 AC: 6652 AN: 152140 Hom.: 459 Cov.: 32 AF XY: 0.0420 AC XY: 3122 AN XY: 74362

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.0149

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0571

Gnomad4 SAS AF: 0.00518

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000515

Gnomad4 OTH AF: 0.0345

Alfa AF: 0.0279 Hom.: 36

Bravo AF: 0.0492

Asia WGS AF: 0.0480 AC: 166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.54
DANN	Benign	0.65

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: rs9332127; hg19: chr10-96707471; COSMIC: COSV53254533; COSMIC: COSV53254533;