10-94982060-A-G

Variant names:

• chr10-94982060-A-G
• rs1934968
• NM_000771.4:c.1149+690A>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.1149+690A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.912 in 152,146 control chromosomes in the GnomAD database, including 63,594 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 0.91 (63594 hom., cov: 31)
• Consequence: CYP2C9 NM_000771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82
• Publications: 5 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C9	NM_000771.4	c.1149+690A>G		intron_variant	Intron 7 of 8	ENST00000260682.8	NP_000762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2C9	ENST00000260682.8	c.1149+690A>G		intron_variant	Intron 7 of 8	1	NM_000771.4	ENSP00000260682.6
CYP2C9	ENST00000643112.1	n.*158+690A>G		intron_variant	Intron 6 of 7			ENSP00000496202.1

Frequencies

GnomAD3 genomes AF: 0.912 AC: 138616 AN: 152028 Hom.: 63529 Cov.: 31

Gnomad AFR AF: 0.977

Gnomad AMI AF: 0.954

Gnomad AMR AF: 0.906

Gnomad ASJ AF: 0.952

Gnomad EAS AF: 0.623

Gnomad SAS AF: 0.880

Gnomad FIN AF: 0.925

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.893

Gnomad OTH AF: 0.916

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

GnomAD4 genome AF: 0.912 AC: 138741 AN: 152146 Hom.: 63594 Cov.: 31 AF XY: 0.911 AC XY: 67718 AN XY: 74362

African (AFR) AF: 0.977 AC: 40590 AN: 41540

American (AMR) AF: 0.906 AC: 13819 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.952 AC: 3304 AN: 3470

East Asian (EAS) AF: 0.623 AC: 3216 AN: 5164

South Asian (SAS) AF: 0.880 AC: 4233 AN: 4808

European-Finnish (FIN) AF: 0.925 AC: 9793 AN: 10586

Middle Eastern (MID) AF: 0.963 AC: 283 AN: 294

European-Non Finnish (NFE) AF: 0.893 AC: 60696 AN: 68006

Other (OTH) AF: 0.917 AC: 1937 AN: 2112

Alfa AF: 0.898 Hom.: 50190

Bravo AF: 0.910

Asia WGS AF: 0.773 AC: 2682 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.0
DANN	Benign	0.36
PhyloP100		-1.8
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: rs1934968; hg19: chr10-96741817;