10-94972974-T-G

Variant summary

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

The NM_000771.4(CYP2C9):c.961+729T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 151,972 control chromosomes in the GnomAD database, including 32,544 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.65 (32544 hom., cov: 31)
• Consequence: CYP2C9 NM_000771.4 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -0.107

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2C9	NM_000771.4	c.961+729T>G		intron_variant		ENST00000260682.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2C9	ENST00000260682.8	c.961+729T>G		intron_variant		1	NM_000771.4	P1
CYP2C9	ENST00000643112.1	c.820-8209T>G		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.646 AC: 98089 AN: 151854 Hom.: 32499 Cov.: 31

Gnomad AFR AF: 0.768

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.633

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

GnomAD4 genome AF: 0.646 AC: 98184 AN: 151972 Hom.: 32544 Cov.: 31 AF XY: 0.642 AC XY: 47695 AN XY: 74286

Gnomad4 AFR AF: 0.768

Gnomad4 AMR AF: 0.506

Gnomad4 ASJ AF: 0.645

Gnomad4 EAS AF: 0.435

Gnomad4 SAS AF: 0.664

Gnomad4 FIN AF: 0.596

Gnomad4 NFE AF: 0.625

Gnomad4 OTH AF: 0.636

Alfa AF: 0.628 Hom.: 57339

Bravo AF: 0.640

Asia WGS AF: 0.583 AC: 2026 AN: 3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Pulmonary disease, chronic obstructive, susceptibility to Other:1

association, no assertion criteria provided

research

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Jul 05, 2022

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	14
Dann	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs1856908; hg19: chr10-96732731;