rs4917623

Positions:

• chr10-94849811-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 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. Variant has been reported in Lovd as Benign (no stars).

• 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

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 10-94849811-T-C is Benign according to our data. Variant chr10-94849811-T-C is described in Lovd as [Benign].
• 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/exons	MANE	Protein	UniProt
CYP2C19	NM_000769.4	c.1150-106T>C		intron_variant		ENST00000371321.9	NP_000760.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2C19	ENST00000371321.9	c.1150-106T>C		intron_variant		1	NM_000769.4	ENSP00000360372	P1
CYP2C19	ENST00000645461.1	n.2061-106T>C		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR exome AF: 0.226

Gnomad4 AMR exome AF: 0.695

Gnomad4 ASJ exome AF: 0.504

Gnomad4 EAS exome AF: 0.542

Gnomad4 SAS exome AF: 0.371

Gnomad4 FIN exome AF: 0.549

Gnomad4 NFE exome AF: 0.535

Gnomad4 OTH exome AF: 0.505

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

Gnomad4 AFR AF: 0.233

Gnomad4 AMR AF: 0.601

Gnomad4 ASJ AF: 0.501

Gnomad4 EAS AF: 0.557

Gnomad4 SAS AF: 0.364

Gnomad4 FIN AF: 0.551

Gnomad4 NFE AF: 0.522

Gnomad4 OTH AF: 0.469

Alfa AF: 0.506 Hom.: 25353

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

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

Other links and lift over

dbSNP: rs4917623; hg19: chr10-96609568;