rs17878649

Positions:

• chr10-94775011-G-A
• chr10-94775011-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.169-47G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00405 in 1,598,240 control chromosomes in the GnomAD database, including 231 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 0.0084 (22 hom., cov: 32)
  • Exomes 𝑓: 0.0036 (209 hom.)
• Consequence: CYP2C19 NM_000769.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.244

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.056 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2C19	NM_000769.4	c.169-47G>A		intron_variant		ENST00000371321.9	NP_000760.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2C19	ENST00000371321.9	c.169-47G>A		intron_variant		1	NM_000769.4	ENSP00000360372.3
CYP2C19	ENST00000480405.2	c.169-47G>A		intron_variant		1		ENSP00000483847.1
ENSG00000276490	ENST00000464755.1	n.932-47G>A		intron_variant		2		ENSP00000483243.1
CYP2C19	ENST00000645461.1	n.1175G>A		non_coding_transcript_exon_variant	1/7

Frequencies

GnomAD3 genomes AF: 0.00834 AC: 1269 AN: 152106 Hom.: 20 Cov.: 32

Gnomad AFR AF: 0.0209

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0616

Gnomad SAS AF: 0.00519

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00764

GnomAD3 exomes AF: 0.00689 AC: 1690 AN: 245252 Hom.: 41 AF XY: 0.00620 AC XY: 821 AN XY: 132338

Gnomad AFR exome AF: 0.0206

Gnomad AMR exome AF: 0.000733

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0637

Gnomad SAS exome AF: 0.00412

Gnomad FIN exome AF: 0.0000955

Gnomad NFE exome AF: 0.000261

Gnomad OTH exome AF: 0.00268

GnomAD4 exome AF: 0.00359 AC: 5194 AN: 1446016 Hom.: 209 Cov.: 28 AF XY: 0.00356 AC XY: 2556 AN XY: 718858

Gnomad4 AFR exome AF: 0.0226

Gnomad4 AMR exome AF: 0.000702

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0924

Gnomad4 SAS exome AF: 0.00348

Gnomad4 FIN exome AF: 0.000132

Gnomad4 NFE exome AF: 0.000112

Gnomad4 OTH exome AF: 0.00546

GnomAD4 genome AF: 0.00839 AC: 1277 AN: 152224 Hom.: 22 Cov.: 32 AF XY: 0.00847 AC XY: 630 AN XY: 74412

Gnomad4 AFR AF: 0.0208

Gnomad4 AMR AF: 0.00183

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0615

Gnomad4 SAS AF: 0.00498

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.0113

Alfa AF: 0.00126 Hom.: 4

Bravo AF: 0.00875

Asia WGS AF: 0.0470 AC: 162 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.6
DANN	Benign	0.26

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: rs17878649; hg19: chr10-96534768;