10-94852614-C-T

Variant names:

• chr10-94852614-C-T
• rs12268020
• NM_000769.4:c.1292-119C>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.1292-119C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 1,076,490 control chromosomes in the GnomAD database, including 22,914 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 0.20 (3271 hom., cov: 32)
  • Exomes 𝑓: 0.20 (19643 hom.)
• Consequence: CYP2C19 NM_000769.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.46
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C19	NM_000769.4	c.1292-119C>T		intron_variant	Intron 8 of 8	ENST00000371321.9	NP_000760.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2C19	ENST00000371321.9	c.1292-119C>T		intron_variant	Intron 8 of 8	1	NM_000769.4	ENSP00000360372.3
ENSG00000276490	ENST00000464755.1	n.*1050-119C>T		intron_variant	Intron 13 of 13	2		ENSP00000483243.1
CYP2C19	ENST00000645461.1	n.2203-119C>T		intron_variant	Intron 6 of 6

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30618 AN: 151992 Hom.: 3270 Cov.: 32

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.00942

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.203

GnomAD4 exome AF: 0.199 AC: 184380 AN: 924380 Hom.: 19643 AF XY: 0.200 AC XY: 94391 AN XY: 472770

African (AFR) AF: 0.225 AC: 4953 AN: 21998

American (AMR) AF: 0.105 AC: 3304 AN: 31590

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 4131 AN: 19180

East Asian (EAS) AF: 0.00904 AC: 327 AN: 36162

South Asian (SAS) AF: 0.168 AC: 10715 AN: 63620

European-Finnish (FIN) AF: 0.191 AC: 8897 AN: 46490

Middle Eastern (MID) AF: 0.212 AC: 628 AN: 2956

European-Non Finnish (NFE) AF: 0.217 AC: 143325 AN: 660590

Other (OTH) AF: 0.194 AC: 8100 AN: 41794

GnomAD4 genome AF: 0.201 AC: 30620 AN: 152110 Hom.: 3271 Cov.: 32 AF XY: 0.198 AC XY: 14715 AN XY: 74380

African (AFR) AF: 0.226 AC: 9381 AN: 41476

American (AMR) AF: 0.133 AC: 2039 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 739 AN: 3466

East Asian (EAS) AF: 0.00944 AC: 49 AN: 5188

South Asian (SAS) AF: 0.163 AC: 783 AN: 4814

European-Finnish (FIN) AF: 0.182 AC: 1932 AN: 10594

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.220 AC: 14963 AN: 67970

Other (OTH) AF: 0.201 AC: 425 AN: 2112

Alfa AF: 0.207 Hom.: 4528

Bravo AF: 0.198

Asia WGS AF: 0.0850 AC: 297 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	0.055
DANN	Benign	0.36
PhyloP100		-3.5
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: rs12268020; hg19: chr10-96612371; COSMIC: COSV64907797;