chr10-94971553-A-G

Variant names:

• chr10-94971553-A-G
• rs9332169
• NM_000771.4:c.820-551A>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.820-551A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0494 in 152,130 control chromosomes in the GnomAD database, including 241 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 0.049 (241 hom., cov: 31)
• Consequence: CYP2C9 NM_000771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.643
• Publications: 7 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C9	NM_000771.4	c.820-551A>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.820-551A>G		intron_variant	Intron 5 of 8	1	NM_000771.4	ENSP00000260682.6
CYP2C9	ENST00000643112.1	n.820-9630A>G		intron_variant	Intron 5 of 7			ENSP00000496202.1

Frequencies

GnomAD3 genomes AF: 0.0495 AC: 7520 AN: 152012 Hom.: 242 Cov.: 31

Gnomad AFR AF: 0.0126

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0492

Gnomad ASJ AF: 0.0824

Gnomad EAS AF: 0.0312

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0560

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0662

Gnomad OTH AF: 0.0527

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

GnomAD4 genome AF: 0.0494 AC: 7513 AN: 152130 Hom.: 241 Cov.: 31 AF XY: 0.0499 AC XY: 3712 AN XY: 74356

African (AFR) AF: 0.0125 AC: 521 AN: 41526

American (AMR) AF: 0.0490 AC: 749 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0824 AC: 286 AN: 3470

East Asian (EAS) AF: 0.0313 AC: 162 AN: 5176

South Asian (SAS) AF: 0.113 AC: 546 AN: 4814

European-Finnish (FIN) AF: 0.0560 AC: 592 AN: 10574

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0662 AC: 4503 AN: 67978

Other (OTH) AF: 0.0512 AC: 108 AN: 2108

Alfa AF: 0.0634 Hom.: 261

Bravo AF: 0.0462

Asia WGS AF: 0.0770 AC: 267 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.66
PhyloP100		-0.64
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: rs9332169; hg19: chr10-96731310;