rs28399513

Variant names:

• chr10-94842641-T-A
• rs28399513
• NM_000769.4:c.962-196T>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.962-196T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,090 control chromosomes in the GnomAD database, including 2,321 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 (2321 hom., cov: 31)
• Consequence: CYP2C19 NM_000769.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.781
• Publications: 13 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C19	NM_000769.4	c.962-196T>A		intron_variant	Intron 6 of 8	ENST00000371321.9	NP_000760.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2C19	ENST00000371321.9	c.962-196T>A		intron_variant	Intron 6 of 8	1	NM_000769.4	ENSP00000360372.3
ENSG00000276490	ENST00000464755.1	n.*720-196T>A		intron_variant	Intron 11 of 13	2		ENSP00000483243.1
CYP2C19	ENST00000645461.1	n.1873-196T>A		intron_variant	Intron 4 of 6

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25373 AN: 151972 Hom.: 2316 Cov.: 31

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.167 AC: 25391 AN: 152090 Hom.: 2321 Cov.: 31 AF XY: 0.171 AC XY: 12723 AN XY: 74364

African (AFR) AF: 0.176 AC: 7301 AN: 41490

American (AMR) AF: 0.129 AC: 1977 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 455 AN: 3466

East Asian (EAS) AF: 0.311 AC: 1605 AN: 5162

South Asian (SAS) AF: 0.330 AC: 1593 AN: 4820

European-Finnish (FIN) AF: 0.182 AC: 1928 AN: 10576

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 10018 AN: 67978

Other (OTH) AF: 0.153 AC: 323 AN: 2114

Alfa AF: 0.154 Hom.: 1130

Bravo AF: 0.160

Asia WGS AF: 0.303 AC: 1050 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.19
DANN	Benign	0.32
PhyloP100		-0.78
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: rs28399513; hg19: chr10-96602398; COSMIC: COSV107469856;