chr10-94988735-G-A

Position:

• chr10-94988735-G-A

Variant summary

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

The NM_000771.4(CYP2C9):​c.1292-112G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 1,141,504 control chromosomes in the GnomAD database, including 18,541 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 0.14 (1845 hom., cov: 32)
  • Exomes 𝑓: 0.18 (16696 hom.)
• Consequence: CYP2C9 NM_000771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2C9	NM_000771.4	c.1292-112G>A		intron_variant		ENST00000260682.8	NP_000762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2C9	ENST00000260682.8	c.1292-112G>A		intron_variant		1	NM_000771.4	ENSP00000260682	P1
CYP2C9	ENST00000643112.1	c.*301-112G>A		intron_variant, NMD_transcript_variant				ENSP00000496202

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20907 AN: 151806 Hom.: 1845 Cov.: 32

Gnomad AFR AF: 0.0361

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.0328

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.205

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.166

GnomAD4 exome AF: 0.175 AC: 173565 AN: 989578 Hom.: 16696 AF XY: 0.176 AC XY: 90163 AN XY: 512588

Gnomad4 AFR exome AF: 0.0334

Gnomad4 AMR exome AF: 0.111

Gnomad4 ASJ exome AF: 0.219

Gnomad4 EAS exome AF: 0.0300

Gnomad4 SAS exome AF: 0.158

Gnomad4 FIN exome AF: 0.176

Gnomad4 NFE exome AF: 0.193

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.138 AC: 20897 AN: 151926 Hom.: 1845 Cov.: 32 AF XY: 0.137 AC XY: 10170 AN XY: 74254

Gnomad4 AFR AF: 0.0360

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.0327

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.174

Gnomad4 NFE AF: 0.193

Gnomad4 OTH AF: 0.163

Alfa AF: 0.190 Hom.: 1871

Bravo AF: 0.132

Asia WGS AF: 0.0930 AC: 326 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.71
DANN	Benign	0.38

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: rs9332238; hg19: chr10-96748492;