rs6583954

Positions:

• chr10-94774506-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000769.4(CYP2C19):​c.169-552C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 157,798 control chromosomes in the GnomAD database, including 2,655 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 0.17 (2570 hom., cov: 32)
  • Exomes 𝑓: 0.14 (85 hom.)
• Consequence: CYP2C19 NM_000769.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.44

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]

MTND4P19 (HGNC:42206): (MT-ND4 pseudogene 19)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2C19	NM_000769.4	c.169-552C>T		intron_variant		ENST00000371321.9	NP_000760.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2C19	ENST00000371321.9	c.169-552C>T		intron_variant		1	NM_000769.4	ENSP00000360372	P1
CYP2C19	ENST00000480405.2	c.169-552C>T		intron_variant		1		ENSP00000483847
MTND4P19	ENST00000446659.1	n.128G>A		non_coding_transcript_exon_variant	1/1
CYP2C19	ENST00000645461.1	n.670C>T		non_coding_transcript_exon_variant	1/7

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26401 AN: 151786 Hom.: 2565 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.153

GnomAD4 exome AF: 0.142 AC: 836 AN: 5894 Hom.: 85 Cov.: 0 AF XY: 0.143 AC XY: 466 AN XY: 3256

Gnomad4 AFR exome AF: 0.150

Gnomad4 AMR exome AF: 0.111

Gnomad4 ASJ exome AF: 0.0357

Gnomad4 EAS exome AF: 0.231

Gnomad4 SAS exome AF: 0.280

Gnomad4 FIN exome AF: 0.125

Gnomad4 NFE exome AF: 0.129

Gnomad4 OTH exome AF: 0.142

GnomAD4 genome AF: 0.174 AC: 26422 AN: 151904 Hom.: 2570 Cov.: 32 AF XY: 0.178 AC XY: 13218 AN XY: 74200

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.310

Gnomad4 SAS AF: 0.330

Gnomad4 FIN AF: 0.187

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.158

Alfa AF: 0.154 Hom.: 1976

Bravo AF: 0.167

Asia WGS AF: 0.305 AC: 1059 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.4
DANN	Benign	0.34

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: rs6583954; hg19: chr10-96534263;