10-94972974-T-G

Variant names:

• chr10-94972974-T-G
• rs1856908
• NM_000771.4:c.961+729T>G

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+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
• Publications: 12 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=-0.98).
• 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 rank	MANE	Protein	UniProt
CYP2C9	NM_000771.4	c.961+729T>G		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+729T>G		intron_variant	Intron 6 of 8	1	NM_000771.4	ENSP00000260682.6
CYP2C9	ENST00000643112.1	n.820-8209T>G		intron_variant	Intron 5 of 7			ENSP00000496202.1

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

African (AFR) AF: 0.768 AC: 31889 AN: 41504

American (AMR) AF: 0.506 AC: 7718 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 2237 AN: 3468

East Asian (EAS) AF: 0.435 AC: 2242 AN: 5150

South Asian (SAS) AF: 0.664 AC: 3198 AN: 4816

European-Finnish (FIN) AF: 0.596 AC: 6289 AN: 10552

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.625 AC: 42471 AN: 67918

Other (OTH) AF: 0.636 AC: 1341 AN: 2110

Alfa AF: 0.629 Hom.: 123307

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

Jul 05, 2022

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Significance: association

Review Status: no assertion criteria provided

Collection Method: research

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	14
DANN	Benign	0.80
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1856908; hg19: chr10-96732731;