10-94946177-A-G

Variant names:

• chr10-94946177-A-G
• rs6583964
• NM_000771.4:c.482-1602A>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.482-1602A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 152,050 control chromosomes in the GnomAD database, including 22,819 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 0.54 (22819 hom., cov: 32)
• Consequence: CYP2C9 NM_000771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.881
• Publications: 2 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C9	NM_000771.4	c.482-1602A>G		intron_variant	Intron 3 of 8	ENST00000260682.8	NP_000762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2C9	ENST00000260682.8	c.482-1602A>G		intron_variant	Intron 3 of 8	1	NM_000771.4	ENSP00000260682.6
CYP2C9	ENST00000473496.1	n.253-1602A>G		intron_variant	Intron 2 of 3	2
CYP2C9	ENST00000643112.1	n.482-1602A>G		intron_variant	Intron 3 of 7			ENSP00000496202.1
CYP2C9	ENST00000645207.1	n.635-1602A>G		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.539 AC: 81825 AN: 151932 Hom.: 22799 Cov.: 32

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.499

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.516

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

GnomAD4 genome AF: 0.539 AC: 81886 AN: 152050 Hom.: 22819 Cov.: 32 AF XY: 0.536 AC XY: 39812 AN XY: 74316

African (AFR) AF: 0.654 AC: 27123 AN: 41450

American (AMR) AF: 0.400 AC: 6111 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.499 AC: 1730 AN: 3468

East Asian (EAS) AF: 0.375 AC: 1942 AN: 5174

South Asian (SAS) AF: 0.527 AC: 2543 AN: 4822

European-Finnish (FIN) AF: 0.513 AC: 5424 AN: 10576

Middle Eastern (MID) AF: 0.490 AC: 143 AN: 292

European-Non Finnish (NFE) AF: 0.518 AC: 35211 AN: 67964

Other (OTH) AF: 0.520 AC: 1098 AN: 2110

Alfa AF: 0.535 Hom.: 2698

Bravo AF: 0.532

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.44
DANN	Benign	0.37
PhyloP100		-0.88
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: rs6583964; hg19: chr10-96705934;