rs1934963

Variant names:

• chr10-94974919-T-C
• rs1934963
• NM_000771.4:c.961+2674T>C

Variant summary

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

The NM_000771.4(CYP2C9):​c.961+2674T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,002 control chromosomes in the GnomAD database, including 2,917 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 (2917 hom., cov: 32)
• Consequence: CYP2C9 NM_000771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.481
• Publications: 16 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C9	NM_000771.4	c.961+2674T>C		intron_variant	Intron 6 of 8	ENST00000260682.8	NP_000762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2C9	ENST00000260682.8	c.961+2674T>C		intron_variant	Intron 6 of 8	1	NM_000771.4	ENSP00000260682.6
CYP2C9	ENST00000643112.1	n.820-6264T>C		intron_variant	Intron 5 of 7			ENSP00000496202.1

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29267 AN: 151884 Hom.: 2915 Cov.: 32

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.0892

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.193 AC: 29291 AN: 152002 Hom.: 2917 Cov.: 32 AF XY: 0.191 AC XY: 14166 AN XY: 74298

African (AFR) AF: 0.214 AC: 8868 AN: 41470

American (AMR) AF: 0.164 AC: 2498 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 775 AN: 3468

East Asian (EAS) AF: 0.0890 AC: 460 AN: 5168

South Asian (SAS) AF: 0.159 AC: 764 AN: 4818

European-Finnish (FIN) AF: 0.189 AC: 2001 AN: 10570

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

European-Non Finnish (NFE) AF: 0.195 AC: 13261 AN: 67964

Other (OTH) AF: 0.207 AC: 437 AN: 2110

Alfa AF: 0.193 Hom.: 4354

Bravo AF: 0.192

Asia WGS AF: 0.145 AC: 507 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.0
DANN	Benign	0.45
PhyloP100		-0.48
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: rs1934963; hg19: chr10-96734676;