10-94815485-C-T

Variant names:

• chr10-94815485-C-T
• rs1322179
• NM_000769.4:c.820-5011C>T

Variant summary

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

The NM_000769.4(CYP2C19):​c.820-5011C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,150 control chromosomes in the GnomAD database, including 2,296 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 0.17 (2296 hom., cov: 30)
• Consequence: CYP2C19 NM_000769.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.340
• Publications: 11 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=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.317 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.820-5011C>T		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.820-5011C>T		intron	N/A	ENSP00000360372.3
	ENSG00000276490	ENST00000464755.1	TSL:2	n.*578-5011C>T		intron	N/A	ENSP00000483243.1
	CYP2C19	ENST00000645461.1		n.1873-27352C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25241 AN: 152032 Hom.: 2292 Cov.: 30

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.166 AC: 25258 AN: 152150 Hom.: 2296 Cov.: 30 AF XY: 0.170 AC XY: 12656 AN XY: 74380

African (AFR) AF: 0.173 AC: 7162 AN: 41506

American (AMR) AF: 0.129 AC: 1972 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 456 AN: 3470

East Asian (EAS) AF: 0.311 AC: 1609 AN: 5166

South Asian (SAS) AF: 0.331 AC: 1595 AN: 4820

European-Finnish (FIN) AF: 0.183 AC: 1934 AN: 10576

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 10020 AN: 68008

Other (OTH) AF: 0.151 AC: 320 AN: 2114

Alfa AF: 0.146 Hom.: 2801

Bravo AF: 0.159

Asia WGS AF: 0.303 AC: 1052 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.52
DANN	Benign	0.17
PhyloP100		-0.34
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: rs1322179; hg19: chr10-96575242;