Genetic Variant CYP2C19:c.1291+122G>C (chr10-94850180-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000769.4(CYP2C19):c.1291+122G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00511 in 1,165,070 control chromosomes in the GnomAD database, including 177 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 0.022 ( 118 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 59 hom. )

Consequence

CYP2C19
NM_000769.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.817

Publications

2 publications found

Variant links:

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]

CYP2C19 links:

ENSG00000276490 (HGNC:):

ENSG00000276490 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.072 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C19	NM_000769.4 link	c.1291+122G>C		intron_variant	Intron 8 of 8	ENST00000371321.9	NP_000760.1	P33261

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CYP2C19	ENST00000371321.9 link	c.1291+122G>C	intron_variant	Intron 8 of 8	1	NM_000769.4	ENSP00000360372.3	P33261
ENSG00000276490	ENST00000464755.1 link	n.*1049+122G>C	intron_variant	Intron 13 of 13	2		ENSP00000483243.1	A0A087X0B3
CYP2C19	ENST00000645461.1 link	n.2202+122G>C	intron_variant	Intron 6 of 6

Frequencies

GnomAD3 genomes

AF:

0.0218

AC:

3309

AN:

152090

Hom.:

118

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0745

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00970

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.000515

Gnomad OTH

AF:

0.0153

GnomAD4 exome

AF:

0.00261

AC:

2644

AN:

1012862

Hom.:

AF XY:

0.00223

AC XY:

1152

AN XY:

517726

show subpopulations

African (AFR)

AF:

0.0716

AC:

1730

AN:

24148

American (AMR)

AF:

0.00574

AC:

208

AN:

36228

Ashkenazi Jewish (ASJ)

AF:

0.00132

AC:

AN:

21242

East Asian (EAS)

AF:

0.00

AC:

AN:

36630

South Asian (SAS)

AF:

0.0000999

AC:

AN:

70046

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42418

Middle Eastern (MID)

AF:

0.00976

AC:

AN:

4404

European-Non Finnish (NFE)

AF:

0.000490

AC:

359

AN:

732480

Other (OTH)

AF:

0.00594

AC:

269

AN:

45266

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

121

241

362

482

603

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

168

224

280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0217

AC:

3304

AN:

152208

Hom.:

118

Cov.:

AF XY:

0.0209

AC XY:

1556

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.0742

AC:

3079

AN:

41512

American (AMR)

AF:

0.00969

AC:

148

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.000864

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000515

AC:

AN:

68014

Other (OTH)

AF:

0.0151

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

151

302

452

603

754

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

152

190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0157

Hom.:

Bravo

AF:

0.0249

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.48

(source)

DANN

Benign

0.44

PhyloP100

-0.82

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over