rs3093099

Positions:

• chr19-15897688-A-G

Variant summary

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

The NM_001082.5(CYP4F2):​c.-1-76T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00636 in 1,558,200 control chromosomes in the GnomAD database, including 453 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 0.029 (234 hom., cov: 32)
  • Exomes 𝑓: 0.0039 (219 hom.)
• Consequence: CYP4F2 NM_001082.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0240

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP4F2	NM_001082.5	c.-1-76T>C		intron_variant		ENST00000221700.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP4F2	ENST00000221700.11	c.-1-76T>C		intron_variant		1	NM_001082.5	P3

Frequencies

GnomAD3 genomes AF: 0.0288 AC: 4374 AN: 152064 Hom.: 229 Cov.: 32

Gnomad AFR AF: 0.0970

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0100

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.00704

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00109

Gnomad OTH AF: 0.0192

GnomAD4 exome AF: 0.00392 AC: 5506 AN: 1406018 Hom.: 219 Cov.: 25 AF XY: 0.00380 AC XY: 2663 AN XY: 700630

Gnomad4 AFR exome AF: 0.101

Gnomad4 AMR exome AF: 0.00777

Gnomad4 ASJ exome AF: 0.0108

Gnomad4 EAS exome AF: 0.000901

Gnomad4 SAS exome AF: 0.00621

Gnomad4 FIN exome AF: 0.0000222

Gnomad4 NFE exome AF: 0.000522

Gnomad4 OTH exome AF: 0.00976

GnomAD4 genome AF: 0.0289 AC: 4399 AN: 152182 Hom.: 234 Cov.: 32 AF XY: 0.0282 AC XY: 2100 AN XY: 74432

Gnomad4 AFR AF: 0.0974

Gnomad4 AMR AF: 0.0100

Gnomad4 ASJ AF: 0.0130

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.00663

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00109

Gnomad4 OTH AF: 0.0190

Alfa AF: 0.0246 Hom.: 10

Bravo AF: 0.0327

Asia WGS AF: 0.0140 AC: 50 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.4
DANN	Benign	0.38

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: rs3093099; hg19: chr19-16008498;