rs28371676

Positions:

• chr10-94942606-T-C

Variant summary

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

The ENST00000461906.1(CYP2C9):​c.*257T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0633 in 569,566 control chromosomes in the GnomAD database, including 1,389 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 0.050 (245 hom., cov: 33)
  • Exomes 𝑓: 0.068 (1144 hom.)
• Consequence: CYP2C9 ENST00000461906.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.186

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 (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.481+265T>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.481+265T>C		intron_variant		1	NM_000771.4	ENSP00000260682	P1

Frequencies

GnomAD3 genomes AF: 0.0497 AC: 7557 AN: 152182 Hom.: 246 Cov.: 33

Gnomad AFR AF: 0.0131

Gnomad AMI AF: 0.0297

Gnomad AMR AF: 0.0491

Gnomad ASJ AF: 0.0827

Gnomad EAS AF: 0.0316

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0560

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0663

Gnomad OTH AF: 0.0527

GnomAD4 exome AF: 0.0683 AC: 28511 AN: 417266 Hom.: 1144 Cov.: 4 AF XY: 0.0700 AC XY: 15392 AN XY: 219752

Gnomad4 AFR exome AF: 0.0153

Gnomad4 AMR exome AF: 0.0460

Gnomad4 ASJ exome AF: 0.0823

Gnomad4 EAS exome AF: 0.0298

Gnomad4 SAS exome AF: 0.110

Gnomad4 FIN exome AF: 0.0644

Gnomad4 NFE exome AF: 0.0693

Gnomad4 OTH exome AF: 0.0644

GnomAD4 genome AF: 0.0496 AC: 7551 AN: 152300 Hom.: 245 Cov.: 33 AF XY: 0.0502 AC XY: 3741 AN XY: 74454

Gnomad4 AFR AF: 0.0131

Gnomad4 AMR AF: 0.0489

Gnomad4 ASJ AF: 0.0827

Gnomad4 EAS AF: 0.0317

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.0560

Gnomad4 NFE AF: 0.0663

Gnomad4 OTH AF: 0.0512

Alfa AF: 0.0579 Hom.: 32

Bravo AF: 0.0465

Asia WGS AF: 0.0770 AC: 268 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	6.2
DANN	Benign	0.75

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: rs28371676; hg19: chr10-96702363;