NM_000771.4:c.1292-109A>T

Variant names:

• chr10-94988738-A-T
• rs1934969
• NM_000771.4:c.1292-109A>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.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
• Publications: 15 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 (AFR) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000771.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2C9	NM_000771.4	MANE Select	c.1292-109A>T		intron	N/A	NP_000762.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2C9	ENST00000260682.8	TSL:1 MANE Select	c.1292-109A>T		intron	N/A	ENSP00000260682.6
	CYP2C9	ENST00000643112.1		n.*301-109A>T		intron	N/A	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

African (AFR) AF: 0.674 AC: 16435 AN: 24374

American (AMR) AF: 0.341 AC: 14799 AN: 43354

Ashkenazi Jewish (ASJ) AF: 0.583 AC: 13339 AN: 22880

East Asian (EAS) AF: 0.441 AC: 16541 AN: 37466

South Asian (SAS) AF: 0.645 AC: 48921 AN: 75902

European-Finnish (FIN) AF: 0.550 AC: 28776 AN: 52322

Middle Eastern (MID) AF: 0.544 AC: 1761 AN: 3240

European-Non Finnish (NFE) AF: 0.579 AC: 404591 AN: 698950

Other (OTH) AF: 0.561 AC: 25254 AN: 45000

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

African (AFR) AF: 0.667 AC: 27663 AN: 41454

American (AMR) AF: 0.447 AC: 6823 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 1997 AN: 3468

East Asian (EAS) AF: 0.407 AC: 2096 AN: 5150

South Asian (SAS) AF: 0.641 AC: 3084 AN: 4812

European-Finnish (FIN) AF: 0.550 AC: 5796 AN: 10538

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

European-Non Finnish (NFE) AF: 0.581 AC: 39447 AN: 67932

Other (OTH) AF: 0.572 AC: 1207 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.5
DANN	Benign	0.32
PhyloP100		-0.28
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: rs1934969; hg19: chr10-96748495; COSMIC: COSV53249486;