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rs17886522

chr10-94850018-A-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_000769.4(CYP2C19):c.1251A>C(p.Gly417=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00406 in 1,613,662 control chromosomes in the GnomAD database, including 233 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. G417G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0084 ( 22 hom., cov: 32)
Exomes 𝑓: 0.0036 ( 211 hom. )

Consequence

CYP2C19
NM_000769.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.31
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 10-94850018-A-C is Benign according to our data. Variant chr10-94850018-A-C is described in ClinVar as [Benign]. Clinvar id is 1276601.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-2.31 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0557 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CYP2C19NM_000769.4 linkuse as main transcriptc.1251A>C p.Gly417= synonymous_variant 8/9 ENST00000371321.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CYP2C19ENST00000371321.9 linkuse as main transcriptc.1251A>C p.Gly417= synonymous_variant 8/91 NM_000769.4 P1
CYP2C19ENST00000645461.1 linkuse as main transcriptn.2162A>C non_coding_transcript_exon_variant 6/7

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00831
AC:
1264
AN:
152118
Hom.:
20
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0208
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00184
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0613
Gnomad SAS
AF:
0.00518
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000250
Gnomad OTH
AF:
0.00765
GnomAD3 exomes
AF:
0.00680
AC:
1709
AN:
251204
Hom.:
42
AF XY:
0.00613
AC XY:
832
AN XY:
135754
show subpopulations
Gnomad AFR exome
AF:
0.0206
Gnomad AMR exome
AF:
0.000753
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0636
Gnomad SAS exome
AF:
0.00412
Gnomad FIN exome
AF:
0.0000924
Gnomad NFE exome
AF:
0.000290
Gnomad OTH exome
AF:
0.00294
GnomAD4 exome
AF:
0.00361
AC:
5276
AN:
1461426
Hom.:
211
Cov.:
32
AF XY:
0.00359
AC XY:
2607
AN XY:
727000
show subpopulations
Gnomad4 AFR exome
AF:
0.0235
Gnomad4 AMR exome
AF:
0.000694
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0924
Gnomad4 SAS exome
AF:
0.00354
Gnomad4 FIN exome
AF:
0.000131
Gnomad4 NFE exome
AF:
0.000118
Gnomad4 OTH exome
AF:
0.00557
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00836
AC:
1273
AN:
152236
Hom.:
22
Cov.:
32
AF XY:
0.00845
AC XY:
629
AN XY:
74448
show subpopulations
Gnomad4 AFR
AF:
0.0208
Gnomad4 AMR
AF:
0.00183
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.0612
Gnomad4 SAS
AF:
0.00498
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000250
Gnomad4 OTH
AF:
0.0114
Alfa
AF:
0.00347
Hom.:
9
Bravo
AF:
0.00875
Asia WGS
AF:
0.0460
AC:
161
AN:
3478
EpiCase
AF:
0.000327
EpiControl
AF:
0.000237

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxFeb 24, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
Cadd
Benign
1.5
Dann
Benign
0.55

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: rs17886522; hg19: chr10-96609775; COSMIC: COSV100990250; API