Variant 10-94762804-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000769.4(CYP2C19):c.99C>T(p.Pro33=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.928 in 1,613,676 control chromosomes in the GnomAD database, including 694,973 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.92 ( 64390 hom., cov: 32)

Exomes 𝑓: 0.93 ( 630583 hom. )

Consequence

CYP2C19
NM_000769.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.13

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 10-94762804-C-T is Benign according to our data. Variant chr10-94762804-C-T is described in ClinVar as [Benign]. Clinvar id is 769226.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-94762804-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.13 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.931 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2C19	NM_000769.4 linkuse as main transcript	c.99C>T	p.Pro33=	synonymous_variant	1/9	ENST00000371321.9	NP_000760.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2C19	ENST00000371321.9 linkuse as main transcript	c.99C>T	p.Pro33=	synonymous_variant	1/9	1	NM_000769.4	ENSP00000360372	P1
CYP2C19	ENST00000480405.2 linkuse as main transcript	c.99C>T	p.Pro33=	synonymous_variant	1/3	1		ENSP00000483847

Frequencies

GnomAD3 genomes

AF:

0.919

AC:

139812

AN:

152058

Hom.:

64355

Cov.:

show subpopulations

Gnomad AFR

AF:

0.887

Gnomad AMI

AF:

0.970

Gnomad AMR

AF:

0.943

Gnomad ASJ

AF:

0.916

Gnomad EAS

AF:

0.900

Gnomad SAS

AF:

0.879

Gnomad FIN

AF:

0.948

Gnomad MID

AF:

0.924

Gnomad NFE

AF:

0.933

Gnomad OTH

AF:

0.920

GnomAD4 exome

AF:

0.929

AC:

1357021

AN:

1461500

Hom.:

630583

Cov.:

AF XY:

0.928

AC XY:

674417

AN XY:

727064

show subpopulations

Gnomad4 AFR exome

AF:

0.875

Gnomad4 AMR exome

AF:

0.958

Gnomad4 ASJ exome

AF:

0.914

Gnomad4 EAS exome

AF:

0.867

Gnomad4 SAS exome

AF:

0.886

Gnomad4 FIN exome

AF:

0.942

Gnomad4 NFE exome

AF:

0.934

Gnomad4 OTH exome

AF:

0.924

GnomAD4 genome

AF:

0.919

AC:

139900

AN:

152176

Hom.:

64390

Cov.:

AF XY:

0.919

AC XY:

68383

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.887

Gnomad4 AMR

AF:

0.944

Gnomad4 ASJ

AF:

0.916

Gnomad4 EAS

AF:

0.900

Gnomad4 SAS

AF:

0.880

Gnomad4 FIN

AF:

0.948

Gnomad4 NFE

AF:

0.933

Gnomad4 OTH

AF:

0.918

Alfa

AF:

0.924

Hom.:

28677

Bravo

AF:

0.919

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 submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.2

Splicing

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over