rs12779363

Positions:

• chr10-94852283-G-A

Variant summary

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

The NM_000769.4(CYP2C19):​c.1292-450G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 152,020 control chromosomes in the GnomAD database, including 3,257 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 0.20 (3257 hom., cov: 32)
• Consequence: CYP2C19 NM_000769.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.271

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2C19	NM_000769.4	c.1292-450G>A		intron_variant		ENST00000371321.9	NP_000760.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2C19	ENST00000371321.9	c.1292-450G>A		intron_variant		1	NM_000769.4	ENSP00000360372.3
ENSG00000276490	ENST00000464755.1	n.*1050-450G>A		intron_variant		2		ENSP00000483243.1
CYP2C19	ENST00000645461.1	n.2203-450G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30515 AN: 151902 Hom.: 3256 Cov.: 32

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.00944

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.201 AC: 30518 AN: 152020 Hom.: 3257 Cov.: 32 AF XY: 0.197 AC XY: 14665 AN XY: 74270

Gnomad4 AFR AF: 0.224

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.00947

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.200

Alfa AF: 0.211 Hom.: 2727

Bravo AF: 0.197

Asia WGS AF: 0.0850 AC: 296 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.20
DANN	Benign	0.43

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: rs12779363; hg19: chr10-96612040;