chr10-94988738-A-T

Position:

• chr10-94988738-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000771.4(CYP2C9):​c.1292-109A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 1,155,416 control chromosomes in the GnomAD database, including 191,731 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 0.58 (26644 hom., cov: 32)
  • Exomes 𝑓: 0.57 (165087 hom.)
• Consequence: CYP2C9 NM_000771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.285

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• 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/exons	MANE	Protein	UniProt
CYP2C9	NM_000771.4	c.1292-109A>T		intron_variant		ENST00000260682.8	NP_000762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2C9	ENST00000260682.8	c.1292-109A>T		intron_variant		1	NM_000771.4	ENSP00000260682.6
CYP2C9	ENST00000643112.1	n.*301-109A>T		intron_variant				ENSP00000496202.1

Frequencies

GnomAD3 genomes AF: 0.585 AC: 88811 AN: 151808 Hom.: 26627 Cov.: 32

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.408

Gnomad SAS AF: 0.640

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.561

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.569

GnomAD4 exome AF: 0.568 AC: 570417 AN: 1003488 Hom.: 165087 AF XY: 0.573 AC XY: 297351 AN XY: 519060

Gnomad4 AFR exome AF: 0.674

Gnomad4 AMR exome AF: 0.341

Gnomad4 ASJ exome AF: 0.583

Gnomad4 EAS exome AF: 0.441

Gnomad4 SAS exome AF: 0.645

Gnomad4 FIN exome AF: 0.550

Gnomad4 NFE exome AF: 0.579

Gnomad4 OTH exome AF: 0.561

GnomAD4 genome AF: 0.585 AC: 88867 AN: 151928 Hom.: 26644 Cov.: 32 AF XY: 0.582 AC XY: 43225 AN XY: 74242

Gnomad4 AFR AF: 0.667

Gnomad4 AMR AF: 0.447

Gnomad4 ASJ AF: 0.576

Gnomad4 EAS AF: 0.407

Gnomad4 SAS AF: 0.641

Gnomad4 FIN AF: 0.550

Gnomad4 NFE AF: 0.581

Gnomad4 OTH AF: 0.572

Alfa AF: 0.588 Hom.: 3305

Bravo AF: 0.577

Asia WGS AF: 0.538 AC: 1872 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	1.5
DANN	Benign	0.32

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

Publications

LitVar

Other links and lift over

dbSNP: rs1934969; hg19: chr10-96748495; COSMIC: COSV53249486;