10-94787706-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.819+5709C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 151,984 control chromosomes in the GnomAD database, including 2,359 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 0.17 (2359 hom., cov: 32)
• Consequence: CYP2C19 NM_000769.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.702

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=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2C19	NM_000769.4	c.819+5709C>T		intron_variant		ENST00000371321.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2C19	ENST00000371321.9	c.819+5709C>T		intron_variant		1	NM_000769.4	P1
CYP2C19	ENST00000645461.1	n.1872+5709C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25424 AN: 151866 Hom.: 2354 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.167 AC: 25442 AN: 151984 Hom.: 2359 Cov.: 32 AF XY: 0.172 AC XY: 12755 AN XY: 74280

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.310

Gnomad4 SAS AF: 0.331

Gnomad4 FIN AF: 0.186

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.153

Alfa AF: 0.155 Hom.: 3507

Bravo AF: 0.160

Asia WGS AF: 0.303 AC: 1052 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	2.2
Dann	Benign	0.56

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: rs12767583; hg19: chr10-96547463;