rs7916649

Positions:

• chr10-94774827-G-A

Variant summary

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

The NM_000769.4(CYP2C19):​c.169-231G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 537,854 control chromosomes in the GnomAD database, including 59,258 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 0.48 (18849 hom., cov: 32)
  • Exomes 𝑓: 0.45 (40409 hom.)
• Consequence: CYP2C19 NM_000769.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.424

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2C19	NM_000769.4	c.169-231G>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.169-231G>A		intron_variant		1	NM_000769.4	ENSP00000360372.3
CYP2C19	ENST00000480405.2	c.169-231G>A		intron_variant		1		ENSP00000483847.1
ENSG00000276490	ENST00000464755.1	n.932-231G>A		intron_variant		2		ENSP00000483243.1
CYP2C19	ENST00000645461.1	n.991G>A		non_coding_transcript_exon_variant	1/7

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73589 AN: 151846 Hom.: 18830 Cov.: 32

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.457

GnomAD4 exome AF: 0.449 AC: 173259 AN: 385890 Hom.: 40409 Cov.: 3 AF XY: 0.458 AC XY: 92972 AN XY: 202870

Gnomad4 AFR exome AF: 0.636

Gnomad4 AMR exome AF: 0.288

Gnomad4 ASJ exome AF: 0.433

Gnomad4 EAS exome AF: 0.448

Gnomad4 SAS exome AF: 0.608

Gnomad4 FIN exome AF: 0.423

Gnomad4 NFE exome AF: 0.429

Gnomad4 OTH exome AF: 0.437

GnomAD4 genome AF: 0.485 AC: 73653 AN: 151964 Hom.: 18849 Cov.: 32 AF XY: 0.485 AC XY: 35978 AN XY: 74238

Gnomad4 AFR AF: 0.636

Gnomad4 AMR AF: 0.335

Gnomad4 ASJ AF: 0.431

Gnomad4 EAS AF: 0.420

Gnomad4 SAS AF: 0.616

Gnomad4 FIN AF: 0.423

Gnomad4 NFE AF: 0.435

Gnomad4 OTH AF: 0.461

Alfa AF: 0.442 Hom.: 30461

Bravo AF: 0.478

Asia WGS AF: 0.533 AC: 1853 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.53
DANN	Benign	0.27

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: rs7916649; hg19: chr10-96534584;