10-94983351-T-C

Position:

• chr10-94983351-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.1149+1981T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0508 in 152,204 control chromosomes in the GnomAD database, including 249 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 0.051 (249 hom., cov: 32)
• Consequence: CYP2C9 NM_000771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.17

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 = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2C9	NM_000771.4	c.1149+1981T>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.1149+1981T>C		intron_variant		1	NM_000771.4	ENSP00000260682.6
CYP2C9	ENST00000643112.1	n.*158+1981T>C		intron_variant				ENSP00000496202.1

Frequencies

GnomAD3 genomes AF: 0.0509 AC: 7738 AN: 152086 Hom.: 250 Cov.: 32

Gnomad AFR AF: 0.0173

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0494

Gnomad ASJ AF: 0.0827

Gnomad EAS AF: 0.0318

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0563

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0662

Gnomad OTH AF: 0.0554

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

GnomAD4 genome AF: 0.0508 AC: 7739 AN: 152204 Hom.: 249 Cov.: 32 AF XY: 0.0516 AC XY: 3840 AN XY: 74438

Gnomad4 AFR AF: 0.0174

Gnomad4 AMR AF: 0.0493

Gnomad4 ASJ AF: 0.0827

Gnomad4 EAS AF: 0.0319

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.0563

Gnomad4 NFE AF: 0.0663

Gnomad4 OTH AF: 0.0539

Alfa AF: 0.0651 Hom.: 482

Bravo AF: 0.0476

Asia WGS AF: 0.0770 AC: 270 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.14
DANN	Benign	0.62

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: rs9332214; hg19: chr10-96743108;