chr10-94972031-A-G

Variant names:

• chr10-94972031-A-G
• rs9332172
• NM_000771.4:c.820-73A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000771.4(CYP2C9):​c.820-73A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 1,547,338 control chromosomes in the GnomAD database, including 30,553 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 0.21 (3584 hom., cov: 32)
  • Exomes 𝑓: 0.19 (26969 hom.)
• Consequence: CYP2C9 NM_000771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C9	NM_000771.4	c.820-73A>G		intron_variant	Intron 5 of 8	ENST00000260682.8	NP_000762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2C9	ENST00000260682.8	c.820-73A>G		intron_variant	Intron 5 of 8	1	NM_000771.4	ENSP00000260682.6
CYP2C9	ENST00000643112.1	n.820-9152A>G		intron_variant	Intron 5 of 7			ENSP00000496202.1

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32083 AN: 151950 Hom.: 3577 Cov.: 32

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.0893

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.215

GnomAD4 exome AF: 0.193 AC: 269688 AN: 1395270 Hom.: 26969 AF XY: 0.192 AC XY: 134193 AN XY: 698250

African (AFR) AF: 0.296 AC: 9440 AN: 31940

American (AMR) AF: 0.123 AC: 5454 AN: 44364

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 5835 AN: 25674

East Asian (EAS) AF: 0.117 AC: 4601 AN: 39230

South Asian (SAS) AF: 0.163 AC: 13776 AN: 84706

European-Finnish (FIN) AF: 0.188 AC: 9988 AN: 53072

Middle Eastern (MID) AF: 0.210 AC: 1189 AN: 5658

European-Non Finnish (NFE) AF: 0.198 AC: 208271 AN: 1052534

Other (OTH) AF: 0.192 AC: 11134 AN: 58092

GnomAD4 genome AF: 0.211 AC: 32117 AN: 152068 Hom.: 3584 Cov.: 32 AF XY: 0.209 AC XY: 15507 AN XY: 74346

African (AFR) AF: 0.279 AC: 11577 AN: 41448

American (AMR) AF: 0.170 AC: 2598 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 772 AN: 3466

East Asian (EAS) AF: 0.0891 AC: 461 AN: 5172

South Asian (SAS) AF: 0.159 AC: 766 AN: 4826

European-Finnish (FIN) AF: 0.189 AC: 1999 AN: 10584

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13263 AN: 67980

Other (OTH) AF: 0.216 AC: 455 AN: 2106

Alfa AF: 0.206 Hom.: 5429

Bravo AF: 0.214

Asia WGS AF: 0.152 AC: 528 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.19
DANN	Benign	0.69
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9332172; hg19: chr10-96731788;