10-94977614-C-T

Variant names:

• chr10-94977614-C-T
• rs1934964
• NM_000771.4:c.962-3569C>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.962-3569C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 151,852 control chromosomes in the GnomAD database, including 26,646 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 0.59 (26646 hom., cov: 31)
• Consequence: CYP2C9 NM_000771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.367
• Publications: 2 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C9	NM_000771.4	c.962-3569C>T		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.962-3569C>T		intron_variant	Intron 6 of 8	1	NM_000771.4	ENSP00000260682.6
CYP2C9	ENST00000643112.1	n.820-3569C>T		intron_variant	Intron 5 of 7			ENSP00000496202.1

Frequencies

GnomAD3 genomes AF: 0.585 AC: 88805 AN: 151732 Hom.: 26629 Cov.: 31

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.642

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.561

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.570

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

GnomAD4 genome AF: 0.585 AC: 88862 AN: 151852 Hom.: 26646 Cov.: 31 AF XY: 0.583 AC XY: 43230 AN XY: 74198

African (AFR) AF: 0.667 AC: 27624 AN: 41400

American (AMR) AF: 0.447 AC: 6809 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 1998 AN: 3466

East Asian (EAS) AF: 0.408 AC: 2106 AN: 5162

South Asian (SAS) AF: 0.642 AC: 3098 AN: 4822

European-Finnish (FIN) AF: 0.551 AC: 5818 AN: 10566

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.581 AC: 39447 AN: 67902

Other (OTH) AF: 0.573 AC: 1209 AN: 2110

Alfa AF: 0.410 Hom.: 975

Bravo AF: 0.577

Asia WGS AF: 0.540 AC: 1877 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	0.79
DANN	Benign	0.23
PhyloP100		-0.37
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: rs1934964; hg19: chr10-96737371;