NM_000771.4:c.168+83T>C

Variant names:

• chr10-94938933-T-C
• rs9332104
• NM_000771.4:c.168+83T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000771.4(CYP2C9):​c.168+83T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 1,439,892 control chromosomes in the GnomAD database, including 29,433 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 0.19 (2965 hom., cov: 32)
  • Exomes 𝑓: 0.20 (26468 hom.)
• Consequence: CYP2C9 NM_000771.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.48
• Publications: 10 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 (NFE) allele frequency at 95% confidence interval = 0.214 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.168+83T>C		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.168+83T>C		intron	N/A	ENSP00000260682.6
	CYP2C9	ENST00000461906.1	TSL:1	c.168+83T>C		intron	N/A	ENSP00000495649.1
	CYP2C9	ENST00000643112.1		n.168+83T>C		intron	N/A	ENSP00000496202.1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29024 AN: 152078 Hom.: 2964 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.00942

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.191

GnomAD4 exome AF: 0.197 AC: 253661 AN: 1287696 Hom.: 26468 AF XY: 0.198 AC XY: 128470 AN XY: 649954

African (AFR) AF: 0.193 AC: 5760 AN: 29886

American (AMR) AF: 0.102 AC: 4511 AN: 44230

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 5372 AN: 25014

East Asian (EAS) AF: 0.00889 AC: 344 AN: 38678

South Asian (SAS) AF: 0.170 AC: 13971 AN: 82306

European-Finnish (FIN) AF: 0.189 AC: 9967 AN: 52670

Middle Eastern (MID) AF: 0.207 AC: 1025 AN: 4946

European-Non Finnish (NFE) AF: 0.212 AC: 202338 AN: 955490

Other (OTH) AF: 0.190 AC: 10373 AN: 54476

GnomAD4 genome AF: 0.191 AC: 29021 AN: 152196 Hom.: 2965 Cov.: 32 AF XY: 0.188 AC XY: 13974 AN XY: 74404

African (AFR) AF: 0.195 AC: 8082 AN: 41526

American (AMR) AF: 0.129 AC: 1972 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 735 AN: 3468

East Asian (EAS) AF: 0.00944 AC: 49 AN: 5190

South Asian (SAS) AF: 0.163 AC: 786 AN: 4818

European-Finnish (FIN) AF: 0.182 AC: 1927 AN: 10596

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14762 AN: 67996

Other (OTH) AF: 0.189 AC: 399 AN: 2116

Alfa AF: 0.202 Hom.: 9081

Bravo AF: 0.186

Asia WGS AF: 0.0830 AC: 290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.41
DANN	Benign	0.52
PhyloP100		-2.5
PromoterAI		-0.0071	Neutral
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: rs9332104; hg19: chr10-96698690; COSMIC: COSV53252617; COSMIC: COSV53252617;