rs12768009

Variant names:

• chr10-94766108-G-A
• rs12768009
• NM_000769.4:c.168+3235G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-94766108-G-A
• chr10-94766108-G-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.168+3235G>A variant causes a intron change. The variant allele was found at a frequency of 0.173 in 152,022 control chromosomes in the GnomAD database, including 2,559 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 (2559 hom., cov: 32)
• Consequence: CYP2C19 NM_000769.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: No conservation score assigned
• Publications: 10 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:):

MTND4P19 (HGNC:42206): (MT-ND4 pseudogene 19)

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 (EAS) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C19	NM_000769.4	c.168+3235G>A		intron_variant	Intron 1 of 8	ENST00000371321.9	NP_000760.1
MTND4P19		n.94766108G>A		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2C19	ENST00000371321.9	c.168+3235G>A		intron_variant	Intron 1 of 8	1	NM_000769.4	ENSP00000360372.3
CYP2C19	ENST00000480405.2	c.168+3235G>A		intron_variant	Intron 1 of 2	1		ENSP00000483847.1
ENSG00000276490	ENST00000464755.1	n.932-8950G>A		intron_variant	Intron 6 of 13	2		ENSP00000483243.1

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26303 AN: 151904 Hom.: 2551 Cov.: 32

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.173 AC: 26327 AN: 152022 Hom.: 2559 Cov.: 32 AF XY: 0.178 AC XY: 13210 AN XY: 74326

African (AFR) AF: 0.188 AC: 7810 AN: 41466

American (AMR) AF: 0.131 AC: 1999 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 457 AN: 3466

East Asian (EAS) AF: 0.374 AC: 1932 AN: 5170

South Asian (SAS) AF: 0.335 AC: 1610 AN: 4812

European-Finnish (FIN) AF: 0.185 AC: 1950 AN: 10518

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10042 AN: 67982

Other (OTH) AF: 0.159 AC: 335 AN: 2110

Alfa AF: 0.154 Hom.: 5133

Bravo AF: 0.166

Asia WGS AF: 0.349 AC: 1211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.2
DANN	Benign	0.74
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: rs12768009; hg19: chr10-96525865;