10-94974582-G-T

Variant names:

• chr10-94974582-G-T
• rs10509680
• NM_000771.4:c.961+2337G>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.961+2337G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0685 in 107,124 control chromosomes in the GnomAD database, including 248 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 0.069 (248 hom., cov: 28)
• Consequence: CYP2C9 NM_000771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.564
• Publications: 19 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C9	NM_000771.4	c.961+2337G>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.961+2337G>T		intron_variant	Intron 6 of 8	1	NM_000771.4	ENSP00000260682.6
CYP2C9	ENST00000643112.1	n.820-6601G>T		intron_variant	Intron 5 of 7			ENSP00000496202.1

Frequencies

GnomAD3 genomes AF: 0.0686 AC: 7347 AN: 107066 Hom.: 249 Cov.: 28

Gnomad AFR AF: 0.0193

Gnomad AMI AF: 0.0433

Gnomad AMR AF: 0.0677

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.0482

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.0836

Gnomad MID AF: 0.0927

Gnomad NFE AF: 0.0857

Gnomad OTH AF: 0.0722

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

GnomAD4 genome AF: 0.0685 AC: 7339 AN: 107124 Hom.: 248 Cov.: 28 AF XY: 0.0708 AC XY: 3606 AN XY: 50942

African (AFR) AF: 0.0192 AC: 506 AN: 26372

American (AMR) AF: 0.0675 AC: 731 AN: 10824

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 285 AN: 2768

East Asian (EAS) AF: 0.0482 AC: 162 AN: 3360

South Asian (SAS) AF: 0.162 AC: 536 AN: 3312

European-Finnish (FIN) AF: 0.0836 AC: 504 AN: 6032

Middle Eastern (MID) AF: 0.0826 AC: 19 AN: 230

European-Non Finnish (NFE) AF: 0.0857 AC: 4463 AN: 52094

Other (OTH) AF: 0.0703 AC: 106 AN: 1508

Alfa AF: 0.0634 Hom.: 1398

Bravo AF: 0.0469

Asia WGS AF: 0.0760 AC: 265 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.45
DANN	Benign	0.11
PhyloP100		-0.56
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: rs10509680; hg19: chr10-96734339;