rs28371683

Variant names:

• chr10-94947751-G-A
• rs28371683
• NM_000771.4:c.482-28G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000260682.8(CYP2C9):​c.482-28G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00048 in 1,609,144 control chromosomes in the GnomAD database, including 2 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 0.0020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00032 (2 hom.)
• Consequence: CYP2C9 ENST00000260682.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.810
• Publications: 3 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS2: High AC in GnomAd4 at 300 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000260682.8. 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.482-28G>A		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.482-28G>A		intron	N/A	ENSP00000260682.6
	CYP2C9	ENST00000473496.1	TSL:2	n.253-28G>A		intron	N/A
	CYP2C9	ENST00000643112.1		n.482-28G>A		intron	N/A	ENSP00000496202.1

Frequencies

GnomAD3 genomes AF: 0.00191 AC: 291 AN: 152072 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00609

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000590

Gnomad ASJ AF: 0.00404

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.000755 AC: 189 AN: 250204 AF XY: 0.000621

Gnomad AFR exome AF: 0.00660

Gnomad AMR exome AF: 0.000465

Gnomad ASJ exome AF: 0.00417

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000177

Gnomad OTH exome AF: 0.000494

GnomAD4 exome AF: 0.000325 AC: 473 AN: 1456954 Hom.: 2 Cov.: 30 AF XY: 0.000298 AC XY: 216 AN XY: 724936

African (AFR) AF: 0.00645 AC: 215 AN: 33314

American (AMR) AF: 0.000403 AC: 18 AN: 44622

Ashkenazi Jewish (ASJ) AF: 0.00430 AC: 112 AN: 26072

East Asian (EAS) AF: 0.00 AC: 0 AN: 39578

South Asian (SAS) AF: 0.0000349 AC: 3 AN: 86024

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53366

Middle Eastern (MID) AF: 0.00259 AC: 11 AN: 4240

European-Non Finnish (NFE) AF: 0.0000550 AC: 61 AN: 1109646

Other (OTH) AF: 0.000865 AC: 52 AN: 60092

GnomAD4 genome AF: 0.00197 AC: 300 AN: 152190 Hom.: 0 Cov.: 32 AF XY: 0.00179 AC XY: 133 AN XY: 74398

African (AFR) AF: 0.00628 AC: 261 AN: 41532

American (AMR) AF: 0.000590 AC: 9 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00404 AC: 14 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68014

Other (OTH) AF: 0.00332 AC: 7 AN: 2110

Alfa AF: 0.00192 Hom.: 0

Bravo AF: 0.00224

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.29
PhyloP100		-0.81
Mutation Taster		=100/0	polymorphism

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: rs28371683; hg19: chr10-96707508;