rs3093099

Variant names:

• chr19-15897688-A-G
• rs3093099
• NM_001082.5:c.-1-76T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CYP4F2	NM_001082.5	c.-1-76T>C		intron_variant	Intron 1 of 12	ENST00000221700.11	NP_001073.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP4F2	ENST00000221700.11	c.-1-76T>C		intron_variant	Intron 1 of 12	1	NM_001082.5	ENSP00000221700.3

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

African (AFR) AF: 0.101 AC: 3193 AN: 31642

American (AMR) AF: 0.00777 AC: 307 AN: 39504

Ashkenazi Jewish (ASJ) AF: 0.0108 AC: 271 AN: 25100

East Asian (EAS) AF: 0.000901 AC: 35 AN: 38850

South Asian (SAS) AF: 0.00621 AC: 517 AN: 83240

European-Finnish (FIN) AF: 0.0000222 AC: 1 AN: 45004

Middle Eastern (MID) AF: 0.0110 AC: 47 AN: 4278

European-Non Finnish (NFE) AF: 0.000522 AC: 564 AN: 1079894

Other (OTH) AF: 0.00976 AC: 571 AN: 58506

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

African (AFR) AF: 0.0974 AC: 4043 AN: 41496

American (AMR) AF: 0.0100 AC: 153 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0130 AC: 45 AN: 3470

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5168

South Asian (SAS) AF: 0.00663 AC: 32 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00109 AC: 74 AN: 67994

Other (OTH) AF: 0.0190 AC: 40 AN: 2110

Alfa AF: 0.0279 Hom.: 13

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
PhyloP100		-0.024
PromoterAI		0.0030	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3093099; hg19: chr19-16008498;