rs17884938

Variant names:

• chr10-94780934-T-A
• rs17884938
• NM_000769.4:c.642+275T>A

Your query was ambiguous. Multiple possible variants found:

• chr10-94780934-T-A
• chr10-94780934-T-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000769.4(CYP2C19):​c.642+275T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0137 in 152,280 control chromosomes in the GnomAD database, including 53 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 0.014 (53 hom., cov: 32)
• Consequence: CYP2C19 NM_000769.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.519
• 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=-0.87).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0137 (2085/152280) while in subpopulation AFR AF = 0.0459 (1907/41572). AF 95% confidence interval is 0.0442. There are 53 homozygotes in GnomAd4. There are 989 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2085 AD gene.

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.642+275T>A		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.642+275T>A		intron	N/A	ENSP00000360372.3	P33261
	ENSG00000276490	ENST00000464755.1	TSL:2	n.*400+275T>A		intron	N/A	ENSP00000483243.1	A0A087X0B3
	CYP2C19	ENST00000883431.1		c.642+275T>A		intron	N/A	ENSP00000553490.1

Frequencies

GnomAD3 genomes AF: 0.0137 AC: 2092 AN: 152162 Hom.: 53 Cov.: 32

Gnomad AFR AF: 0.0462

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00766

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000485

Gnomad OTH AF: 0.0105

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

GnomAD4 genome AF: 0.0137 AC: 2085 AN: 152280 Hom.: 53 Cov.: 32 AF XY: 0.0133 AC XY: 989 AN XY: 74456

African (AFR) AF: 0.0459 AC: 1907 AN: 41572

American (AMR) AF: 0.00765 AC: 117 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000485 AC: 33 AN: 68022

Other (OTH) AF: 0.0104 AC: 22 AN: 2114

Alfa AF: 0.000778 Hom.: 0

Bravo AF: 0.0157

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.65
DANN	Benign	0.79
PhyloP100		0.52
Mutation Taster		=100/0	polymorphism

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: rs17884938; hg19: chr10-96540691;