rs11188092

Positions:

• chr10-94837994-A-C
• chr10-94837994-A-T

Variant summary

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

The ENST00000371321.9(CYP2C19):​c.962-4843A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 151,884 control chromosomes in the GnomAD database, including 2,994 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 0.19 (2994 hom., cov: 31)
• Consequence: CYP2C19 ENST00000371321.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.127

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2C19	NM_000769.4	c.962-4843A>C		intron_variant		ENST00000371321.9	NP_000760.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2C19	ENST00000371321.9	c.962-4843A>C		intron_variant		1	NM_000769.4	ENSP00000360372	P1
CYP2C19	ENST00000645461.1	n.1873-4843A>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29152 AN: 151766 Hom.: 2993 Cov.: 31

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.00947

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.192 AC: 29152 AN: 151884 Hom.: 2994 Cov.: 31 AF XY: 0.189 AC XY: 14037 AN XY: 74252

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.00949

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.174

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.194

Alfa AF: 0.191 Hom.: 522

Bravo AF: 0.188

Asia WGS AF: 0.0850 AC: 294 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.5
DANN	Benign	0.34

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: rs11188092; hg19: chr10-96597751;