10-94946177-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.482-1602A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 152,050 control chromosomes in the GnomAD database, including 22,819 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 0.54 (22819 hom., cov: 32)
• Consequence: CYP2C9 NM_000771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.881

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2C9	NM_000771.4	c.482-1602A>G		intron_variant		ENST00000260682.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2C9	ENST00000260682.8	c.482-1602A>G		intron_variant		1	NM_000771.4	P1
CYP2C9	ENST00000643112.1	c.482-1602A>G		intron_variant, NMD_transcript_variant
CYP2C9	ENST00000473496.1	n.253-1602A>G		intron_variant, non_coding_transcript_variant		2
CYP2C9	ENST00000645207.1	n.635-1602A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.539 AC: 81825 AN: 151932 Hom.: 22799 Cov.: 32

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.499

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.516

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

GnomAD4 genome AF: 0.539 AC: 81886 AN: 152050 Hom.: 22819 Cov.: 32 AF XY: 0.536 AC XY: 39812 AN XY: 74316

Gnomad4 AFR AF: 0.654

Gnomad4 AMR AF: 0.400

Gnomad4 ASJ AF: 0.499

Gnomad4 EAS AF: 0.375

Gnomad4 SAS AF: 0.527

Gnomad4 FIN AF: 0.513

Gnomad4 NFE AF: 0.518

Gnomad4 OTH AF: 0.520

Alfa AF: 0.535 Hom.: 2698

Bravo AF: 0.532

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.44
Dann	Benign	0.37

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: rs6583964; hg19: chr10-96705934;