chr10-94965778-A-C

Position:

• chr10-94965778-A-C

Variant summary

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

The NM_000771.4(CYP2C9):​c.820-6326A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,062 control chromosomes in the GnomAD database, including 2,878 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 (2878 hom., cov: 32)
• Consequence: CYP2C9 NM_000771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.829

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 (AFR) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2C9	NM_000771.4	c.820-6326A>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.820-6326A>C		intron_variant		1	NM_000771.4	ENSP00000260682	P1
CYP2C9	ENST00000643112.1	c.820-15405A>C		intron_variant, NMD_transcript_variant				ENSP00000496202

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29011 AN: 151942 Hom.: 2875 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.0902

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.191 AC: 29037 AN: 152062 Hom.: 2878 Cov.: 32 AF XY: 0.188 AC XY: 13996 AN XY: 74326

Gnomad4 AFR AF: 0.214

Gnomad4 AMR AF: 0.164

Gnomad4 ASJ AF: 0.222

Gnomad4 EAS AF: 0.0900

Gnomad4 SAS AF: 0.159

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.209

Alfa AF: 0.191 Hom.: 3956

Bravo AF: 0.192

Asia WGS AF: 0.145 AC: 505 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.75
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: rs4917639; hg19: chr10-96725535;