chr10-94816433-A-C

Variant names:

• chr10-94816433-A-C
• rs10509678
• NM_000769.4:c.820-4063A>C

Variant summary

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

The NM_000769.4(CYP2C19):​c.820-4063A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0476 in 152,214 control chromosomes in the GnomAD database, including 235 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 0.048 (235 hom., cov: 30)
• Consequence: CYP2C19 NM_000769.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55
• Publications: 7 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 = 0.107 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.820-4063A>C		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.820-4063A>C		intron	N/A	ENSP00000360372.3
	ENSG00000276490	ENST00000464755.1	TSL:2	n.*578-4063A>C		intron	N/A	ENSP00000483243.1
	CYP2C19	ENST00000645461.1		n.1873-26404A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0477 AC: 7250 AN: 152096 Hom.: 236 Cov.: 30

Gnomad AFR AF: 0.0124

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0465

Gnomad ASJ AF: 0.0802

Gnomad EAS AF: 0.0376

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0503

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0633

Gnomad OTH AF: 0.0541

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

GnomAD4 genome AF: 0.0476 AC: 7243 AN: 152214 Hom.: 235 Cov.: 30 AF XY: 0.0481 AC XY: 3582 AN XY: 74426

African (AFR) AF: 0.0123 AC: 512 AN: 41558

American (AMR) AF: 0.0463 AC: 709 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0802 AC: 278 AN: 3468

East Asian (EAS) AF: 0.0377 AC: 195 AN: 5178

South Asian (SAS) AF: 0.114 AC: 552 AN: 4824

European-Finnish (FIN) AF: 0.0503 AC: 532 AN: 10572

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

European-Non Finnish (NFE) AF: 0.0634 AC: 4308 AN: 67996

Other (OTH) AF: 0.0526 AC: 111 AN: 2112

Alfa AF: 0.0627 Hom.: 547

Bravo AF: 0.0444

Asia WGS AF: 0.0750 AC: 261 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	12
DANN	Benign	0.33
PhyloP100		1.5
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: rs10509678; hg19: chr10-96576190;