chr10-94781616-A-G

Position:

• chr10-94781616-A-G

Variant summary

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

The NM_000769.4(CYP2C19):​c.643-205A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0776 in 152,130 control chromosomes in the GnomAD database, including 534 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 0.078 (534 hom., cov: 32)
• Consequence: CYP2C19 NM_000769.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450

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 = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2C19	NM_000769.4	c.643-205A>G		intron_variant		ENST00000371321.9	NP_000760.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2C19	ENST00000371321.9	c.643-205A>G		intron_variant		1	NM_000769.4	ENSP00000360372	P1
CYP2C19	ENST00000645461.1	n.1696-205A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0775 AC: 11781 AN: 152012 Hom.: 532 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0550

Gnomad ASJ AF: 0.0804

Gnomad EAS AF: 0.0995

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.0515

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0666

Gnomad OTH AF: 0.0752

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

GnomAD4 genome AF: 0.0776 AC: 11799 AN: 152130 Hom.: 534 Cov.: 32 AF XY: 0.0778 AC XY: 5781 AN XY: 74350

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.0549

Gnomad4 ASJ AF: 0.0804

Gnomad4 EAS AF: 0.0996

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.0515

Gnomad4 NFE AF: 0.0667

Gnomad4 OTH AF: 0.0773

Alfa AF: 0.0740 Hom.: 141

Bravo AF: 0.0771

Asia WGS AF: 0.130 AC: 451 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.69

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: rs7088784; hg19: chr10-96541373;