10-94763288-A-T

Variant names:

• chr10-94763288-A-T
• rs10509676
• NM_000769.4:c.168+415A>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.168+415A>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 152,044 control chromosomes in the GnomAD database, including 2,332 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 (2332 hom., cov: 32)
• Consequence: CYP2C19 NM_000769.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71
• Publications: 8 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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C19	NM_000769.4	c.168+415A>T		intron_variant	Intron 1 of 8	ENST00000371321.9	NP_000760.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2C19	ENST00000371321.9	c.168+415A>T		intron_variant	Intron 1 of 8	1	NM_000769.4	ENSP00000360372.3
CYP2C19	ENST00000480405.2	c.168+415A>T		intron_variant	Intron 1 of 2	1		ENSP00000483847.1
ENSG00000276490	ENST00000464755.1	n.932-11770A>T		intron_variant	Intron 6 of 13	2		ENSP00000483243.1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25252 AN: 151926 Hom.: 2328 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.166 AC: 25269 AN: 152044 Hom.: 2332 Cov.: 32 AF XY: 0.170 AC XY: 12638 AN XY: 74296

African (AFR) AF: 0.173 AC: 7194 AN: 41516

American (AMR) AF: 0.129 AC: 1965 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 455 AN: 3458

East Asian (EAS) AF: 0.312 AC: 1611 AN: 5158

South Asian (SAS) AF: 0.329 AC: 1584 AN: 4812

European-Finnish (FIN) AF: 0.184 AC: 1941 AN: 10540

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

European-Non Finnish (NFE) AF: 0.147 AC: 10010 AN: 67970

Other (OTH) AF: 0.151 AC: 319 AN: 2112

Alfa AF: 0.0742 Hom.: 95

Bravo AF: 0.159

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.026
DANN	Benign	0.55
PhyloP100		-1.7
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: rs10509676; hg19: chr10-96523045;