rs12572351

Positions:

• chr10-94943463-G-A
• chr10-94943463-G-C

Variant summary

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

The NM_000771.4(CYP2C9):​c.481+1122G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,132 control chromosomes in the GnomAD database, including 1,938 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 0.14 (1938 hom., cov: 32)
• Consequence: CYP2C9 NM_000771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.581

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2C9	NM_000771.4	c.481+1122G>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.481+1122G>A		intron_variant		1	NM_000771.4	ENSP00000260682	P1
CYP2C9	ENST00000643112.1	c.481+1122G>A		intron_variant, NMD_transcript_variant				ENSP00000496202
CYP2C9	ENST00000473496.1	n.252+1122G>A		intron_variant, non_coding_transcript_variant		2
CYP2C9	ENST00000645207.1	n.634+1122G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21250 AN: 152014 Hom.: 1935 Cov.: 32

Gnomad AFR AF: 0.0411

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.140 AC: 21260 AN: 152132 Hom.: 1938 Cov.: 32 AF XY: 0.145 AC XY: 10766 AN XY: 74352

Gnomad4 AFR AF: 0.0411

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.319

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.133

Alfa AF: 0.140 Hom.: 381

Bravo AF: 0.127

Asia WGS AF: 0.294 AC: 1020 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.3
DANN	Benign	0.15

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: rs12572351; hg19: chr10-96703220;