dbSNP rs6583954: CYP2C19:c.169-552C>T (chr10-94774506-C-T) – 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.169-552C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 157,798 control chromosomes in the GnomAD database, including 2,655 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 ( 2570 hom., cov: 32)

Exomes 𝑓: 0.14 ( 85 hom. )

Consequence

CYP2C19
NM_000769.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -6.44

Publications

17 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:

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

MTND4P19 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=-0.75).

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 link	c.169-552C>T		intron_variant	Intron 1 of 8	ENST00000371321.9	NP_000760.1	P33261
MTND4P19		n.94774506C>T		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2C19	ENST00000371321.9 link	c.169-552C>T		intron_variant	Intron 1 of 8	1	NM_000769.4	ENSP00000360372.3		P33261
ENSG00000276490	ENST00000464755.1 link	n.932-552C>T		intron_variant	Intron 6 of 13	2		ENSP00000483243.1		A0A087X0B3

Frequencies

GnomAD3 genomes

AF:

0.174

AC:

26401

AN:

151786

Hom.:

2565

Cov.:

show subpopulations

Gnomad AFR

AF:

0.196

Gnomad AMI

AF:

0.181

Gnomad AMR

AF:

0.133

Gnomad ASJ

AF:

0.132

Gnomad EAS

AF:

0.311

Gnomad SAS

AF:

0.329

Gnomad FIN

AF:

0.187

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.149

Gnomad OTH

AF:

0.153

GnomAD4 exome

AF:

0.142

AC:

836

AN:

5894

Hom.:

Cov.:

AF XY:

0.143

AC XY:

466

AN XY:

3256

show subpopulations

African (AFR)

AF:

0.150

AC:

AN:

American (AMR)

AF:

0.111

AC:

132

AN:

1186

Ashkenazi Jewish (ASJ)

AF:

0.0357

AC:

AN:

East Asian (EAS)

AF:

0.231

AC:

AN:

108

South Asian (SAS)

AF:

0.280

AC:

157

AN:

560

European-Finnish (FIN)

AF:

0.125

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.129

AC:

486

AN:

3760

Other (OTH)

AF:

0.142

AC:

AN:

204

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

107

142

178

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.174

AC:

26422

AN:

151904

Hom.:

2570

Cov.:

AF XY:

0.178

AC XY:

13218

AN XY:

74200

show subpopulations

African (AFR)

AF:

0.196

AC:

8129

AN:

41450

American (AMR)

AF:

0.133

AC:

2035

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.132

AC:

459

AN:

3468

East Asian (EAS)

AF:

0.310

AC:

1605

AN:

5172

South Asian (SAS)

AF:

0.330

AC:

1583

AN:

4798

European-Finnish (FIN)

AF:

0.187

AC:

1965

AN:

10482

Middle Eastern (MID)

AF:

0.0918

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.149

AC:

10121

AN:

67952

Other (OTH)

AF:

0.158

AC:

333

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1085

2169

3254

4338

5423

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

308

616

924

1232

1540

<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:

0.153

Hom.:

2444

Bravo

AF:

0.167

Asia WGS

AF:

0.305

AC:

1059

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

1.4

(source)

DANN

Benign

0.34

PhyloP100

-6.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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