rs1934967

Variant names:

• chr10-94981669-C-T
• rs1934967
• NM_000771.4:c.1149+299C>T

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+299C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,014 control chromosomes in the GnomAD database, including 3,425 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 0.19 (3425 hom., cov: 32)
• Consequence: CYP2C9 NM_000771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.657
• Publications: 18 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C9	NM_000771.4	c.1149+299C>T		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+299C>T		intron_variant	Intron 7 of 8	1	NM_000771.4	ENSP00000260682.6
CYP2C9	ENST00000643112.1	n.*158+299C>T		intron_variant	Intron 6 of 7			ENSP00000496202.1

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28849 AN: 151896 Hom.: 3412 Cov.: 32

Gnomad AFR AF: 0.0622

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.190 AC: 28878 AN: 152014 Hom.: 3425 Cov.: 32 AF XY: 0.195 AC XY: 14474 AN XY: 74292

African (AFR) AF: 0.0621 AC: 2579 AN: 41504

American (AMR) AF: 0.330 AC: 5037 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 624 AN: 3462

East Asian (EAS) AF: 0.186 AC: 962 AN: 5172

South Asian (SAS) AF: 0.187 AC: 900 AN: 4810

European-Finnish (FIN) AF: 0.308 AC: 3249 AN: 10534

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.219 AC: 14906 AN: 67960

Other (OTH) AF: 0.180 AC: 380 AN: 2112

Alfa AF: 0.210 Hom.: 6114

Bravo AF: 0.187

Asia WGS AF: 0.169 AC: 586 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	1.1
DANN	Benign	0.68
PhyloP100		-0.66
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: rs1934967; hg19: chr10-96741426;