rs1934966

chr10-94979135-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.962-2048T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0879 in 152,142 control chromosomes in the GnomAD database, including 754 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 0.088 (754 hom., cov: 32)
• Consequence: CYP2C9 NM_000771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.761

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 (NFE) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2C9	NM_000771.4	c.962-2048T>C		intron_variant		ENST00000260682.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2C9	ENST00000260682.8	c.962-2048T>C		intron_variant		1	NM_000771.4	P1
CYP2C9	ENST00000643112.1	c.820-2048T>C		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0880 AC: 13385 AN: 152024 Hom.: 754 Cov.: 32

Gnomad AFR AF: 0.0235

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.0977

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0390

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.0879 AC: 13380 AN: 152142 Hom.: 754 Cov.: 32 AF XY: 0.0867 AC XY: 6445 AN XY: 74346

Gnomad4 AFR AF: 0.0235

Gnomad4 AMR AF: 0.0975

Gnomad4 ASJ AF: 0.135

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0390

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.111

Alfa AF: 0.0996 Hom.: 107

Bravo AF: 0.0859

Asia WGS AF: 0.0160 AC: 56 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.9
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: rs1934966; hg19: chr10-96738892;