rs4917623

Variant names:

• chr10-94849811-T-C
• rs4917623
• NM_000769.4:c.1150-106T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000769.4(CYP2C19):​c.1150-106T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 1,342,868 control chromosomes in the GnomAD database, including 182,700 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 0.45 (16740 hom., cov: 29)
  • Exomes 𝑓: 0.52 (165960 hom.)
• Consequence: CYP2C19 NM_000769.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.832
• Publications: 29 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C19	NM_000769.4	c.1150-106T>C		intron_variant	Intron 7 of 8	ENST00000371321.9	NP_000760.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2C19	ENST00000371321.9	c.1150-106T>C		intron_variant	Intron 7 of 8	1	NM_000769.4	ENSP00000360372.3
ENSG00000276490	ENST00000464755.1	n.*908-106T>C		intron_variant	Intron 12 of 13	2		ENSP00000483243.1
CYP2C19	ENST00000645461.1	n.2061-106T>C		intron_variant	Intron 5 of 6

Frequencies

GnomAD3 genomes AF: 0.448 AC: 67913 AN: 151620 Hom.: 16734 Cov.: 29

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.474

GnomAD4 exome AF: 0.521 AC: 620666 AN: 1191130 Hom.: 165960 AF XY: 0.515 AC XY: 311618 AN XY: 605406

African (AFR) AF: 0.226 AC: 6258 AN: 27728

American (AMR) AF: 0.695 AC: 30271 AN: 43546

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 12134 AN: 24068

East Asian (EAS) AF: 0.542 AC: 20793 AN: 38372

South Asian (SAS) AF: 0.371 AC: 29342 AN: 79134

European-Finnish (FIN) AF: 0.549 AC: 26918 AN: 49006

Middle Eastern (MID) AF: 0.468 AC: 2395 AN: 5122

European-Non Finnish (NFE) AF: 0.535 AC: 466609 AN: 872748

Other (OTH) AF: 0.505 AC: 25946 AN: 51406

GnomAD4 genome AF: 0.448 AC: 67925 AN: 151738 Hom.: 16740 Cov.: 29 AF XY: 0.450 AC XY: 33381 AN XY: 74126

African (AFR) AF: 0.233 AC: 9639 AN: 41432

American (AMR) AF: 0.601 AC: 9142 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1734 AN: 3464

East Asian (EAS) AF: 0.557 AC: 2863 AN: 5136

South Asian (SAS) AF: 0.364 AC: 1750 AN: 4808

European-Finnish (FIN) AF: 0.551 AC: 5791 AN: 10506

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.522 AC: 35419 AN: 67874

Other (OTH) AF: 0.469 AC: 989 AN: 2108

Alfa AF: 0.496 Hom.: 37696

Bravo AF: 0.449

Asia WGS AF: 0.428 AC: 1492 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.11
DANN	Benign	0.33
PhyloP100		-0.83
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4917623; hg19: chr10-96609568;