rs11188092

Variant names:

• chr10-94837994-A-C
• rs11188092
• NM_000769.4:c.962-4843A>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000769.4(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 NM_000769.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.127
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CYP2C19	NM_000769.4	c.962-4843A>C		intron_variant	Intron 6 of 8	ENST00000371321.9	NP_000760.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2C19	ENST00000371321.9	c.962-4843A>C		intron_variant	Intron 6 of 8	1	NM_000769.4	ENSP00000360372.3
ENSG00000276490	ENST00000464755.1	n.*720-4843A>C		intron_variant	Intron 11 of 13	2		ENSP00000483243.1
CYP2C19	ENST00000645461.1	n.1873-4843A>C		intron_variant	Intron 4 of 6

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

African (AFR) AF: 0.222 AC: 9193 AN: 41368

American (AMR) AF: 0.127 AC: 1938 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 737 AN: 3468

East Asian (EAS) AF: 0.00949 AC: 49 AN: 5164

South Asian (SAS) AF: 0.163 AC: 784 AN: 4816

European-Finnish (FIN) AF: 0.174 AC: 1843 AN: 10564

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 13961 AN: 67932

Other (OTH) AF: 0.194 AC: 409 AN: 2108

Alfa AF: 0.190 Hom.: 1063

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
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11188092; hg19: chr10-96597751;