NM_000769.4:c.962-3084G>A

Variant names:

• chr10-94839753-G-A
• rs7915414
• NM_000769.4:c.962-3084G>A

Variant summary

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

The NM_000769.4(CYP2C19):​c.962-3084G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 152,092 control chromosomes in the GnomAD database, including 5,313 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 0.26 (5313 hom., cov: 32)
• Consequence: CYP2C19 NM_000769.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71
• Publications: 3 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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000769.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2C19	NM_000769.4	MANE Select	c.962-3084G>A		intron	N/A	NP_000760.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2C19	ENST00000371321.9	TSL:1 MANE Select	c.962-3084G>A		intron	N/A	ENSP00000360372.3
	ENSG00000276490	ENST00000464755.1	TSL:2	n.*720-3084G>A		intron	N/A	ENSP00000483243.1
	CYP2C19	ENST00000645461.1		n.1873-3084G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38930 AN: 151974 Hom.: 5300 Cov.: 32

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.234

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

GnomAD4 genome AF: 0.256 AC: 38980 AN: 152092 Hom.: 5313 Cov.: 32 AF XY: 0.260 AC XY: 19356 AN XY: 74370

African (AFR) AF: 0.319 AC: 13215 AN: 41456

American (AMR) AF: 0.190 AC: 2906 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 752 AN: 3472

East Asian (EAS) AF: 0.412 AC: 2130 AN: 5170

South Asian (SAS) AF: 0.452 AC: 2176 AN: 4818

European-Finnish (FIN) AF: 0.234 AC: 2477 AN: 10590

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.214 AC: 14575 AN: 67986

Other (OTH) AF: 0.241 AC: 509 AN: 2114

Alfa AF: 0.233 Hom.: 628

Bravo AF: 0.250

Asia WGS AF: 0.440 AC: 1527 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.90
DANN	Benign	0.39
PhyloP100		-1.7
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: rs7915414; hg19: chr10-96599510;