rs3093135

Positions:

• chr19-15893561-A-T

Variant summary

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

The NM_001082.5(CYP4F2):​c.344-979T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,194 control chromosomes in the GnomAD database, including 1,809 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 0.15 (1809 hom., cov: 32)
• Consequence: CYP4F2 NM_001082.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.199

Genes affected

CYP4F2 (HGNC:2645): (cytochrome P450 family 4 subfamily F member 2) 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. The enzyme starts the process of inactivating and degrading leukotriene B4, a potent mediator of inflammation. This gene is part of a cluster of cytochrome P450 genes on chromosome 19. Another member of this family, CYP4F11, is approximately 16 kb away. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP4F2	NM_001082.5	c.344-979T>A		intron_variant		ENST00000221700.11	NP_001073.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP4F2	ENST00000221700.11	c.344-979T>A		intron_variant		1	NM_001082.5	ENSP00000221700	P3

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22896 AN: 152074 Hom.: 1808 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.0934

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.0849

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.185

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.151 AC: 22913 AN: 152194 Hom.: 1809 Cov.: 32 AF XY: 0.149 AC XY: 11105 AN XY: 74408

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.0857

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.111

Gnomad4 NFE AF: 0.166

Gnomad4 OTH AF: 0.186

Alfa AF: 0.162 Hom.: 271

Bravo AF: 0.152

Asia WGS AF: 0.141 AC: 491 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.0
DANN	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs3093135; hg19: chr19-16004371;