rs11592737

chr10-94843657-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.1149+633A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 152,176 control chromosomes in the GnomAD database, including 3,279 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 (3279 hom., cov: 33)
• Consequence: CYP2C19 NM_000769.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2C19	NM_000769.4	c.1149+633A>G		intron_variant		ENST00000371321.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2C19	ENST00000371321.9	c.1149+633A>G		intron_variant		1	NM_000769.4	P1
CYP2C19	ENST00000645461.1	n.2060+633A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30639 AN: 152058 Hom.: 3278 Cov.: 33

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.261

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.00942

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.203

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

GnomAD4 genome AF: 0.201 AC: 30642 AN: 152176 Hom.: 3279 Cov.: 33 AF XY: 0.198 AC XY: 14723 AN XY: 74436

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.00944

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.201

Alfa AF: 0.209 Hom.: 5774

Bravo AF: 0.198

Asia WGS AF: 0.0860 AC: 299 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.13
Dann	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11592737; hg19: chr10-96603414;