chr10-94820383-T-G

Variant names:

• chr10-94820383-T-G
• rs28399511
• NM_000769.4:c.820-113T>G

Variant summary

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

The NM_000769.4(CYP2C19):​c.820-113T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0618 in 1,253,734 control chromosomes in the GnomAD database, including 2,780 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 0.048 (235 hom., cov: 30)
  • Exomes 𝑓: 0.064 (2545 hom.)
• Consequence: CYP2C19 NM_000769.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C19	NM_000769.4	c.820-113T>G		intron_variant	Intron 5 of 8	ENST00000371321.9	NP_000760.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2C19	ENST00000371321.9	c.820-113T>G		intron_variant	Intron 5 of 8	1	NM_000769.4	ENSP00000360372.3
ENSG00000276490	ENST00000464755.1	n.*578-113T>G		intron_variant	Intron 10 of 13	2		ENSP00000483243.1
CYP2C19	ENST00000645461.1	n.1873-22454T>G		intron_variant	Intron 4 of 6

Frequencies

GnomAD3 genomes AF: 0.0477 AC: 7257 AN: 152196 Hom.: 236 Cov.: 30

Gnomad AFR AF: 0.0124

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0467

Gnomad ASJ AF: 0.0804

Gnomad EAS AF: 0.0375

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0505

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0633

Gnomad OTH AF: 0.0536

GnomAD4 exome AF: 0.0638 AC: 70217 AN: 1101420 Hom.: 2545 AF XY: 0.0652 AC XY: 36460 AN XY: 559414

African (AFR) AF: 0.0127 AC: 332 AN: 26082

American (AMR) AF: 0.0386 AC: 1420 AN: 36820

Ashkenazi Jewish (ASJ) AF: 0.0815 AC: 1777 AN: 21792

East Asian (EAS) AF: 0.0400 AC: 1455 AN: 36358

South Asian (SAS) AF: 0.110 AC: 7954 AN: 72006

European-Finnish (FIN) AF: 0.0575 AC: 2684 AN: 46704

Middle Eastern (MID) AF: 0.0736 AC: 371 AN: 5044

European-Non Finnish (NFE) AF: 0.0634 AC: 51236 AN: 808076

Other (OTH) AF: 0.0616 AC: 2988 AN: 48538

GnomAD4 genome AF: 0.0476 AC: 7250 AN: 152314 Hom.: 235 Cov.: 30 AF XY: 0.0481 AC XY: 3585 AN XY: 74486

African (AFR) AF: 0.0123 AC: 511 AN: 41578

American (AMR) AF: 0.0465 AC: 712 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0804 AC: 279 AN: 3470

East Asian (EAS) AF: 0.0376 AC: 195 AN: 5188

South Asian (SAS) AF: 0.114 AC: 552 AN: 4824

European-Finnish (FIN) AF: 0.0505 AC: 536 AN: 10614

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0633 AC: 4309 AN: 68020

Other (OTH) AF: 0.0521 AC: 110 AN: 2112

Alfa AF: 0.0540 Hom.: 31

Bravo AF: 0.0444

Asia WGS AF: 0.0780 AC: 272 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.0
DANN	Benign	0.32
PhyloP100		-0.066
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs28399511; hg19: chr10-96580140;