rs4388808

Positions:

• chr10-94776299-A-G
• chr10-94776299-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000480405.2(CYP2C19):​c.*752A>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 0.165 in 152,108 control chromosomes in the GnomAD database, including 2,288 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 0.16 (2288 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: CYP2C19 ENST00000480405.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2C19	NM_000769.4	c.481+760A>G		intron_variant		ENST00000371321.9	NP_000760.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2C19	ENST00000480405.2	c.*752A>G		3_prime_UTR_variant	3/3	1		ENSP00000483847
CYP2C19	ENST00000371321.9	c.481+760A>G		intron_variant		1	NM_000769.4	ENSP00000360372	P1
CYP2C19	ENST00000645461.1	n.1534+760A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25052 AN: 151990 Hom.: 2293 Cov.: 33

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.184

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.165 AC: 25041 AN: 152108 Hom.: 2288 Cov.: 33 AF XY: 0.163 AC XY: 12123 AN XY: 74340

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.182

Gnomad4 EAS AF: 0.371

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.181

Alfa AF: 0.173 Hom.: 4577

Bravo AF: 0.173

Asia WGS AF: 0.242 AC: 841 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.24
DANN	Benign	0.82

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

Publications

LitVar

Other links and lift over

dbSNP: rs4388808; hg19: chr10-96536056;