rs7088784

Variant names:

• chr10-94781616-A-G
• rs7088784
• NM_000769.4:c.643-205A>G

Variant summary

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

The NM_000769.4(CYP2C19):​c.643-205A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0776 in 152,130 control chromosomes in the GnomAD database, including 534 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 0.078 (534 hom., cov: 32)
• Consequence: CYP2C19 NM_000769.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450
• Publications: 14 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.113 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2C19	NM_000769.4	MANE Select	c.643-205A>G		intron	N/A	NP_000760.1	P33261

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2C19	ENST00000371321.9	TSL:1 MANE Select	c.643-205A>G		intron	N/A	ENSP00000360372.3	P33261
	ENSG00000276490	ENST00000464755.1	TSL:2	n.*401-205A>G		intron	N/A	ENSP00000483243.1	A0A087X0B3
	CYP2C19	ENST00000883431.1		c.643-205A>G		intron	N/A	ENSP00000553490.1

Frequencies

GnomAD3 genomes AF: 0.0775 AC: 11781 AN: 152012 Hom.: 532 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0550

Gnomad ASJ AF: 0.0804

Gnomad EAS AF: 0.0995

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.0515

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0666

Gnomad OTH AF: 0.0752

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

GnomAD4 genome AF: 0.0776 AC: 11799 AN: 152130 Hom.: 534 Cov.: 32 AF XY: 0.0778 AC XY: 5781 AN XY: 74350

African (AFR) AF: 0.103 AC: 4300 AN: 41550

American (AMR) AF: 0.0549 AC: 838 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0804 AC: 279 AN: 3468

East Asian (EAS) AF: 0.0996 AC: 516 AN: 5182

South Asian (SAS) AF: 0.121 AC: 582 AN: 4824

European-Finnish (FIN) AF: 0.0515 AC: 543 AN: 10536

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0667 AC: 4532 AN: 67990

Other (OTH) AF: 0.0773 AC: 163 AN: 2110

Alfa AF: 0.0745 Hom.: 256

Bravo AF: 0.0771

Asia WGS AF: 0.130 AC: 451 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.69
PhyloP100		-0.045
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: rs7088784; hg19: chr10-96541373;