10-94962487-G-A

Position:

• chr10-94962487-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000771.4(CYP2C9):​c.820-9617G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00318 in 152,116 control chromosomes in the GnomAD database, including 4 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 0.0032 (4 hom., cov: 32)
• Consequence: CYP2C9 NM_000771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.309

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=-0.94).
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00318 (484/152116) while in subpopulation EAS AF= 0.0249 (129/5182). AF 95% confidence interval is 0.0214. There are 4 homozygotes in gnomad4. There are 348 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 484 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2C9	NM_000771.4	c.820-9617G>A		intron_variant		ENST00000260682.8	NP_000762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2C9	ENST00000260682.8	c.820-9617G>A		intron_variant		1	NM_000771.4	ENSP00000260682	P1
CYP2C9	ENST00000643112.1	c.819+13203G>A		intron_variant, NMD_transcript_variant				ENSP00000496202

Frequencies

GnomAD3 genomes AF: 0.00318 AC: 484 AN: 151998 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000658

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.0248

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.0293

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.00239

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

GnomAD4 genome AF: 0.00318 AC: 484 AN: 152116 Hom.: 4 Cov.: 32 AF XY: 0.00468 AC XY: 348 AN XY: 74346

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.0000657

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.0249

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.0293

Gnomad4 NFE AF: 0.000309

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.000471 Hom.: 0

Bravo AF: 0.00133

Asia WGS AF: 0.0160 AC: 55 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.6
DANN	Benign	0.28

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: rs9332146; hg19: chr10-96722244;