rs28399511

Positions:

• chr10-94820383-T-G

Variant summary

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

The NM_000769.4(CYP2C19):​c.820-113T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0618 in 1,253,734 control chromosomes in the GnomAD database, including 2,780 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 0.048 (235 hom., cov: 30)
  • Exomes 𝑓: 0.064 (2545 hom.)
• Consequence: CYP2C19 NM_000769.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2C19	NM_000769.4	c.820-113T>G		intron_variant		ENST00000371321.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2C19	ENST00000371321.9	c.820-113T>G		intron_variant		1	NM_000769.4	P1
CYP2C19	ENST00000645461.1	n.1873-22454T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0477 AC: 7257 AN: 152196 Hom.: 236 Cov.: 30

Gnomad AFR AF: 0.0124

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0467

Gnomad ASJ AF: 0.0804

Gnomad EAS AF: 0.0375

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0505

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0633

Gnomad OTH AF: 0.0536

GnomAD4 exome AF: 0.0638 AC: 70217 AN: 1101420 Hom.: 2545 AF XY: 0.0652 AC XY: 36460 AN XY: 559414

Gnomad4 AFR exome AF: 0.0127

Gnomad4 AMR exome AF: 0.0386

Gnomad4 ASJ exome AF: 0.0815

Gnomad4 EAS exome AF: 0.0400

Gnomad4 SAS exome AF: 0.110

Gnomad4 FIN exome AF: 0.0575

Gnomad4 NFE exome AF: 0.0634

Gnomad4 OTH exome AF: 0.0616

GnomAD4 genome AF: 0.0476 AC: 7250 AN: 152314 Hom.: 235 Cov.: 30 AF XY: 0.0481 AC XY: 3585 AN XY: 74486

Gnomad4 AFR AF: 0.0123

Gnomad4 AMR AF: 0.0465

Gnomad4 ASJ AF: 0.0804

Gnomad4 EAS AF: 0.0376

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.0505

Gnomad4 NFE AF: 0.0633

Gnomad4 OTH AF: 0.0521

Alfa AF: 0.0552 Hom.: 29

Bravo AF: 0.0444

Asia WGS AF: 0.0780 AC: 272 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.0
DANN	Benign	0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs28399511; hg19: chr10-96580140;