chr10-94945466-A-T

Position:

• chr10-94945466-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.482-2313A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,264 control chromosomes in the GnomAD database, including 2,942 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 0.19 (2942 hom., cov: 33)
• Consequence: CYP2C9 NM_000771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.317

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2C9	NM_000771.4	c.482-2313A>T		intron_variant		ENST00000260682.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2C9	ENST00000260682.8	c.482-2313A>T		intron_variant		1	NM_000771.4	P1
CYP2C9	ENST00000643112.1	c.482-2313A>T		intron_variant, NMD_transcript_variant
CYP2C9	ENST00000473496.1	n.253-2313A>T		intron_variant, non_coding_transcript_variant		2
CYP2C9	ENST00000645207.1	n.635-2313A>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28888 AN: 152146 Hom.: 2941 Cov.: 33

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.00943

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.190 AC: 28887 AN: 152264 Hom.: 2942 Cov.: 33 AF XY: 0.187 AC XY: 13910 AN XY: 74460

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.00945

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.187

Alfa AF: 0.0888 Hom.: 150

Bravo AF: 0.185

Asia WGS AF: 0.0830 AC: 289 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.2
DANN	Benign	0.44

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: rs7089580; hg19: chr10-96705223;