rs2475376

Positions:

• chr10-94952643-A-G

Variant summary

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

The NM_000771.4(CYP2C9):​c.819+3359A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.838 in 152,140 control chromosomes in the GnomAD database, including 53,624 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 0.84 (53624 hom., cov: 32)
• Consequence: CYP2C9 NM_000771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.200

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=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2C9	NM_000771.4	c.819+3359A>G		intron_variant		ENST00000260682.8	NP_000762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2C9	ENST00000260682.8	c.819+3359A>G		intron_variant		1	NM_000771.4	ENSP00000260682	P1
CYP2C9	ENST00000643112.1	c.819+3359A>G		intron_variant, NMD_transcript_variant				ENSP00000496202

Frequencies

GnomAD3 genomes AF: 0.837 AC: 127316 AN: 152022 Hom.: 53563 Cov.: 32

Gnomad AFR AF: 0.832

Gnomad AMI AF: 0.891

Gnomad AMR AF: 0.836

Gnomad ASJ AF: 0.826

Gnomad EAS AF: 0.622

Gnomad SAS AF: 0.853

Gnomad FIN AF: 0.905

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.847

Gnomad OTH AF: 0.814

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

GnomAD4 genome AF: 0.838 AC: 127440 AN: 152140 Hom.: 53624 Cov.: 32 AF XY: 0.838 AC XY: 62348 AN XY: 74360

Gnomad4 AFR AF: 0.832

Gnomad4 AMR AF: 0.836

Gnomad4 ASJ AF: 0.826

Gnomad4 EAS AF: 0.622

Gnomad4 SAS AF: 0.853

Gnomad4 FIN AF: 0.905

Gnomad4 NFE AF: 0.847

Gnomad4 OTH AF: 0.817

Alfa AF: 0.843 Hom.: 69683

Bravo AF: 0.828

Asia WGS AF: 0.750 AC: 2602 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.0
DANN	Benign	0.61

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: rs2475376; hg19: chr10-96712400;