rs17885098

Variant names:

• chr10-94762804-C-T
• rs17885098
• NM_000769.4:c.99C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_000769.4(CYP2C19):​c.99C>T​(p.Pro33Pro) 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
• Publications: 46 publications found

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]

ENSG00000276490 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 769226.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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 rank	MANE	Protein	UniProt
CYP2C19	NM_000769.4	c.99C>T	p.Pro33Pro	synonymous_variant	Exon 1 of 9	ENST00000371321.9	NP_000760.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2C19	ENST00000371321.9	c.99C>T	p.Pro33Pro	synonymous_variant	Exon 1 of 9	1	NM_000769.4	ENSP00000360372.3
CYP2C19	ENST00000480405.2	c.99C>T	p.Pro33Pro	synonymous_variant	Exon 1 of 3	1		ENSP00000483847.1
ENSG00000276490	ENST00000464755.1	n.932-12254C>T		intron_variant	Intron 6 of 13	2		ENSP00000483243.1

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

African (AFR) AF: 0.875 AC: 29292 AN: 33472

American (AMR) AF: 0.958 AC: 42809 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.914 AC: 23888 AN: 26132

East Asian (EAS) AF: 0.867 AC: 34421 AN: 39692

South Asian (SAS) AF: 0.886 AC: 76376 AN: 86246

European-Finnish (FIN) AF: 0.942 AC: 50279 AN: 53394

Middle Eastern (MID) AF: 0.917 AC: 5279 AN: 5758

European-Non Finnish (NFE) AF: 0.934 AC: 1038852 AN: 1111718

Other (OTH) AF: 0.924 AC: 55825 AN: 60386

GnomAD4 genome AF: 0.919 AC: 139900 AN: 152176 Hom.: 64390 Cov.: 32 AF XY: 0.919 AC XY: 68383 AN XY: 74382

African (AFR) AF: 0.887 AC: 36808 AN: 41520

American (AMR) AF: 0.944 AC: 14433 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.916 AC: 3179 AN: 3472

East Asian (EAS) AF: 0.900 AC: 4658 AN: 5174

South Asian (SAS) AF: 0.880 AC: 4227 AN: 4806

European-Finnish (FIN) AF: 0.948 AC: 10021 AN: 10570

Middle Eastern (MID) AF: 0.932 AC: 274 AN: 294

European-Non Finnish (NFE) AF: 0.933 AC: 63474 AN: 68018

Other (OTH) AF: 0.918 AC: 1943 AN: 2116

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

May 12, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.2
PhyloP100		-1.1
PromoterAI		0.012	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17885098; hg19: chr10-96522561;