rs7916649

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000371321.9(CYP2C19):​c.169-231G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 537,854 control chromosomes in the GnomAD database, including 59,258 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 0.48 ( 18849 hom., cov: 32)
Exomes 𝑓: 0.45 ( 40409 hom. )

Consequence

CYP2C19
ENST00000371321.9 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.424
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-1.0).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CYP2C19NM_000769.4 linkuse as main transcriptc.169-231G>A intron_variant ENST00000371321.9 NP_000760.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CYP2C19ENST00000371321.9 linkuse as main transcriptc.169-231G>A intron_variant 1 NM_000769.4 ENSP00000360372 P1
CYP2C19ENST00000480405.2 linkuse as main transcriptc.169-231G>A intron_variant 1 ENSP00000483847
CYP2C19ENST00000645461.1 linkuse as main transcriptn.991G>A non_coding_transcript_exon_variant 1/7

Frequencies

GnomAD3 genomes
AF:
0.485
AC:
73589
AN:
151846
Hom.:
18830
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.636
Gnomad AMI
AF:
0.476
Gnomad AMR
AF:
0.335
Gnomad ASJ
AF:
0.431
Gnomad EAS
AF:
0.421
Gnomad SAS
AF:
0.616
Gnomad FIN
AF:
0.423
Gnomad MID
AF:
0.421
Gnomad NFE
AF:
0.435
Gnomad OTH
AF:
0.457
GnomAD4 exome
AF:
0.449
AC:
173259
AN:
385890
Hom.:
40409
Cov.:
3
AF XY:
0.458
AC XY:
92972
AN XY:
202870
show subpopulations
Gnomad4 AFR exome
AF:
0.636
Gnomad4 AMR exome
AF:
0.288
Gnomad4 ASJ exome
AF:
0.433
Gnomad4 EAS exome
AF:
0.448
Gnomad4 SAS exome
AF:
0.608
Gnomad4 FIN exome
AF:
0.423
Gnomad4 NFE exome
AF:
0.429
Gnomad4 OTH exome
AF:
0.437
GnomAD4 genome
AF:
0.485
AC:
73653
AN:
151964
Hom.:
18849
Cov.:
32
AF XY:
0.485
AC XY:
35978
AN XY:
74238
show subpopulations
Gnomad4 AFR
AF:
0.636
Gnomad4 AMR
AF:
0.335
Gnomad4 ASJ
AF:
0.431
Gnomad4 EAS
AF:
0.420
Gnomad4 SAS
AF:
0.616
Gnomad4 FIN
AF:
0.423
Gnomad4 NFE
AF:
0.435
Gnomad4 OTH
AF:
0.461
Alfa
AF:
0.442
Hom.:
30461
Bravo
AF:
0.478
Asia WGS
AF:
0.533
AC:
1853
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
CADD
Benign
0.53
DANN
Benign
0.27

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs7916649; hg19: chr10-96534584; API