rs17443251

chr10-94948133-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.642+194T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0915 in 152,094 control chromosomes in the GnomAD database, including 820 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 0.091 (820 hom., cov: 32)
• Consequence: CYP2C9 NM_000771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2C9	NM_000771.4	c.642+194T>C		intron_variant		ENST00000260682.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2C9	ENST00000260682.8	c.642+194T>C		intron_variant		1	NM_000771.4	P1
CYP2C9	ENST00000643112.1	c.642+194T>C		intron_variant, NMD_transcript_variant
CYP2C9	ENST00000473496.1	n.413+194T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0916 AC: 13915 AN: 151976 Hom.: 820 Cov.: 32

Gnomad AFR AF: 0.0237

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.0996

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0395

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.112

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0915 AC: 13910 AN: 152094 Hom.: 820 Cov.: 32 AF XY: 0.0908 AC XY: 6747 AN XY: 74330

Gnomad4 AFR AF: 0.0237

Gnomad4 AMR AF: 0.0994

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.000967

Gnomad4 SAS AF: 0.0395

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.130

Gnomad4 OTH AF: 0.111

Alfa AF: 0.127 Hom.: 1341

Bravo AF: 0.0880

Asia WGS AF: 0.0170 AC: 61 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.24
Dann	Benign	0.68

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: rs17443251; hg19: chr10-96707890;