10-94852614-C-T

Position:

• chr10-94852614-C-T

Variant summary

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

The NM_000769.4(CYP2C19):​c.1292-119C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 1,076,490 control chromosomes in the GnomAD database, including 22,914 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 (3271 hom., cov: 32)
  • Exomes 𝑓: 0.20 (19643 hom.)
• Consequence: CYP2C19 NM_000769.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.46

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2C19	NM_000769.4	c.1292-119C>T		intron_variant		ENST00000371321.9	NP_000760.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2C19	ENST00000371321.9	c.1292-119C>T		intron_variant		1	NM_000769.4	ENSP00000360372.3
ENSG00000276490	ENST00000464755.1	n.*1050-119C>T		intron_variant		2		ENSP00000483243.1
CYP2C19	ENST00000645461.1	n.2203-119C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30618 AN: 151992 Hom.: 3270 Cov.: 32

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.00942

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.203

GnomAD4 exome AF: 0.199 AC: 184380 AN: 924380 Hom.: 19643 AF XY: 0.200 AC XY: 94391 AN XY: 472770

Gnomad4 AFR exome AF: 0.225

Gnomad4 AMR exome AF: 0.105

Gnomad4 ASJ exome AF: 0.215

Gnomad4 EAS exome AF: 0.00904

Gnomad4 SAS exome AF: 0.168

Gnomad4 FIN exome AF: 0.191

Gnomad4 NFE exome AF: 0.217

Gnomad4 OTH exome AF: 0.194

GnomAD4 genome AF: 0.201 AC: 30620 AN: 152110 Hom.: 3271 Cov.: 32 AF XY: 0.198 AC XY: 14715 AN XY: 74380

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.00944

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.201

Alfa AF: 0.207 Hom.: 3235

Bravo AF: 0.198

Asia WGS AF: 0.0850 AC: 297 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.055
DANN	Benign	0.36

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: rs12268020; hg19: chr10-96612371; COSMIC: COSV64907797;