rs17880188

Positions:

• chr10-94850180-G-C

Variant summary

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

The NM_000769.4(CYP2C19):​c.1291+122G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00511 in 1,165,070 control chromosomes in the GnomAD database, including 177 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 0.022 (118 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (59 hom.)
• Consequence: CYP2C19 NM_000769.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.817

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.072 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2C19	NM_000769.4	c.1291+122G>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.1291+122G>C		intron_variant		1	NM_000769.4	ENSP00000360372	P1
CYP2C19	ENST00000645461.1	n.2202+122G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0218 AC: 3309 AN: 152090 Hom.: 118 Cov.: 32

Gnomad AFR AF: 0.0745

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00970

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.000515

Gnomad OTH AF: 0.0153

GnomAD4 exome AF: 0.00261 AC: 2644 AN: 1012862 Hom.: 59 AF XY: 0.00223 AC XY: 1152 AN XY: 517726

Gnomad4 AFR exome AF: 0.0716

Gnomad4 AMR exome AF: 0.00574

Gnomad4 ASJ exome AF: 0.00132

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000999

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000490

Gnomad4 OTH exome AF: 0.00594

GnomAD4 genome AF: 0.0217 AC: 3304 AN: 152208 Hom.: 118 Cov.: 32 AF XY: 0.0209 AC XY: 1556 AN XY: 74420

Gnomad4 AFR AF: 0.0742

Gnomad4 AMR AF: 0.00969

Gnomad4 ASJ AF: 0.000864

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000515

Gnomad4 OTH AF: 0.0151

Alfa AF: 0.0157 Hom.: 8

Bravo AF: 0.0249

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.48
DANN	Benign	0.44

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: rs17880188; hg19: chr10-96609937;