chr10-94775986-A-G

Variant names:

• chr10-94775986-A-G
• rs4244284
• ENST00000480405.2:c.*439A>G

Variant summary

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

The ENST00000480405.2(CYP2C19):​c.*439A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 196,442 control chromosomes in the GnomAD database, including 23,037 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 (16809 hom., cov: 32)
  • Exomes 𝑓: 0.52 (6228 hom.)
• Consequence: CYP2C19 ENST00000480405.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99

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

Verdict is Benign. Variant got -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 = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C19	NM_000769.4	c.481+447A>G		intron_variant	Intron 3 of 8	ENST00000371321.9	NP_000760.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2C19	ENST00000480405.2	c.*439A>G		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000483847.1
CYP2C19	ENST00000371321.9	c.481+447A>G		intron_variant	Intron 3 of 8	1	NM_000769.4	ENSP00000360372.3
ENSG00000276490	ENST00000464755.1	n.*239+447A>G		intron_variant	Intron 8 of 13	2		ENSP00000483243.1
CYP2C19	ENST00000645461.1	n.1534+447A>G		intron_variant	Intron 2 of 6

Frequencies

GnomAD3 genomes AF: 0.448 AC: 67986 AN: 151818 Hom.: 16803 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.500

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.476

GnomAD4 exome AF: 0.521 AC: 23184 AN: 44506 Hom.: 6228 Cov.: 0 AF XY: 0.507 AC XY: 11605 AN XY: 22906

Gnomad4 AFR exome AF: 0.227

Gnomad4 AMR exome AF: 0.649

Gnomad4 ASJ exome AF: 0.504

Gnomad4 EAS exome AF: 0.571

Gnomad4 SAS exome AF: 0.387

Gnomad4 FIN exome AF: 0.563

Gnomad4 NFE exome AF: 0.534

Gnomad4 OTH exome AF: 0.540

GnomAD4 genome AF: 0.448 AC: 67999 AN: 151936 Hom.: 16809 Cov.: 32 AF XY: 0.450 AC XY: 33417 AN XY: 74252

Gnomad4 AFR AF: 0.233

Gnomad4 AMR AF: 0.602

Gnomad4 ASJ AF: 0.500

Gnomad4 EAS AF: 0.558

Gnomad4 SAS AF: 0.364

Gnomad4 FIN AF: 0.545

Gnomad4 NFE AF: 0.522

Gnomad4 OTH AF: 0.471

Alfa AF: 0.471 Hom.: 2265

Bravo AF: 0.449

Asia WGS AF: 0.428 AC: 1489 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	0.039
DANN	Benign	0.47

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: rs4244284; hg19: chr10-96535743;