10-94775986-A-G

Variant names:

• chr10-94775986-A-G
• rs4244284
• ENST00000480405.2:c.*439A>G

Variant summary

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

The ENST00000480405.2(CYP2C19):​c.*439A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 196,442 control chromosomes in the GnomAD database, including 23,037 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 0.45 (16809 hom., cov: 32)
  • Exomes 𝑓: 0.52 (6228 hom.)
• Consequence: CYP2C19 ENST00000480405.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99
• Publications: 3 publications found

Genes affected

CYP2C19 (HGNC:2621): (cytochrome P450 family 2 subfamily C member 19) 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 is known to metabolize many xenobiotics, including the anticonvulsive drug mephenytoin, omeprazole, diazepam and some barbiturates. Polymorphism within this gene is associated with variable ability to metabolize mephenytoin, known as the poor metabolizer and extensive metabolizer phenotypes. The gene is located within a cluster of cytochrome P450 genes on chromosome 10q24. [provided by RefSeq, Jul 2008]

ENSG00000276490 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000480405.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2C19	NM_000769.4	MANE Select	c.481+447A>G		intron	N/A	NP_000760.1	P33261

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2C19	ENST00000480405.2	TSL:1	c.*439A>G		3_prime_UTR	Exon 3 of 3	ENSP00000483847.1	A0A087X125
	CYP2C19	ENST00000371321.9	TSL:1 MANE Select	c.481+447A>G		intron	N/A	ENSP00000360372.3	P33261
	ENSG00000276490	ENST00000464755.1	TSL:2	n.*239+447A>G		intron	N/A	ENSP00000483243.1	A0A087X0B3

Frequencies

GnomAD3 genomes AF: 0.448 AC: 67986 AN: 151818 Hom.: 16803 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.500

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.476

GnomAD4 exome AF: 0.521 AC: 23184 AN: 44506 Hom.: 6228 Cov.: 0 AF XY: 0.507 AC XY: 11605 AN XY: 22906

African (AFR) AF: 0.227 AC: 214 AN: 942

American (AMR) AF: 0.649 AC: 2342 AN: 3608

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 452 AN: 896

East Asian (EAS) AF: 0.571 AC: 1567 AN: 2742

South Asian (SAS) AF: 0.387 AC: 2174 AN: 5614

European-Finnish (FIN) AF: 0.563 AC: 712 AN: 1264

Middle Eastern (MID) AF: 0.452 AC: 56 AN: 124

European-Non Finnish (NFE) AF: 0.534 AC: 14433 AN: 27032

Other (OTH) AF: 0.540 AC: 1234 AN: 2284

GnomAD4 genome AF: 0.448 AC: 67999 AN: 151936 Hom.: 16809 Cov.: 32 AF XY: 0.450 AC XY: 33417 AN XY: 74252

African (AFR) AF: 0.233 AC: 9664 AN: 41480

American (AMR) AF: 0.602 AC: 9197 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1736 AN: 3470

East Asian (EAS) AF: 0.558 AC: 2882 AN: 5166

South Asian (SAS) AF: 0.364 AC: 1753 AN: 4818

European-Finnish (FIN) AF: 0.545 AC: 5714 AN: 10486

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.522 AC: 35456 AN: 67934

Other (OTH) AF: 0.471 AC: 992 AN: 2104

Alfa AF: 0.464 Hom.: 2329

Bravo AF: 0.449

Asia WGS AF: 0.428 AC: 1489 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.039
DANN	Benign	0.47
PhyloP100		-2.0
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: rs4244284; hg19: chr10-96535743;