10-94986227-A-T

Position:

• chr10-94986227-A-T

Variant summary

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

The NM_000771.4(CYP2C9):​c.1291+53A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0635 in 1,569,750 control chromosomes in the GnomAD database, including 3,622 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 (244 hom., cov: 32)
  • Exomes 𝑓: 0.065 (3378 hom.)
• Consequence: CYP2C9 NM_000771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32

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=-0.84).
• 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.1291+53A>T		intron_variant		ENST00000260682.8	NP_000762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2C9	ENST00000260682.8	c.1291+53A>T		intron_variant		1	NM_000771.4	ENSP00000260682	P1
CYP2C9	ENST00000643112.1	c.*300+53A>T		intron_variant, NMD_transcript_variant				ENSP00000496202

Frequencies

GnomAD3 genomes AF: 0.0497 AC: 7550 AN: 152052 Hom.: 245 Cov.: 32

Gnomad AFR AF: 0.0131

Gnomad AMI AF: 0.0297

Gnomad AMR AF: 0.0491

Gnomad ASJ AF: 0.0824

Gnomad EAS AF: 0.0316

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0561

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0663

Gnomad OTH AF: 0.0531

GnomAD4 exome AF: 0.0650 AC: 92095 AN: 1417582 Hom.: 3378 AF XY: 0.0664 AC XY: 47012 AN XY: 708256

Gnomad4 AFR exome AF: 0.0147

Gnomad4 AMR exome AF: 0.0396

Gnomad4 ASJ exome AF: 0.0831

Gnomad4 EAS exome AF: 0.0302

Gnomad4 SAS exome AF: 0.110

Gnomad4 FIN exome AF: 0.0631

Gnomad4 NFE exome AF: 0.0649

Gnomad4 OTH exome AF: 0.0647

GnomAD4 genome AF: 0.0496 AC: 7544 AN: 152168 Hom.: 244 Cov.: 32 AF XY: 0.0501 AC XY: 3730 AN XY: 74384

Gnomad4 AFR AF: 0.0131

Gnomad4 AMR AF: 0.0490

Gnomad4 ASJ AF: 0.0824

Gnomad4 EAS AF: 0.0317

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.0561

Gnomad4 NFE AF: 0.0663

Gnomad4 OTH AF: 0.0516

Alfa AF: 0.0595 Hom.: 43

Bravo AF: 0.0465

Asia WGS AF: 0.0770 AC: 268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.25
DANN	Benign	0.63

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: rs9332230; hg19: chr10-96745984;