rs17885098

chr10-94762804-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.13

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]

ACMG classification

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	UniProt
CYP2C19	NM_000769.4	c.99C>T	p.Pro33=	synonymous_variant	1/9	ENST00000371321.9

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.919 AC: 139812 AN: 152058 Hom.: 64355 Cov.: 32

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.: 49 AF XY: 0.928 AC XY: 674417 AN XY: 727064

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.: 32 AF XY: 0.919 AC XY: 68383 AN XY: 74382

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

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 12, 2018

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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

Other links and lift over

dbSNP: rs17885098; hg19: chr10-96522561;