rs3093200

Variant names:

• chr19-15878779-G-T
• rs3093200
• NM_001082.5:c.1555C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-15878779-G-T
• chr19-15878779-G-A
• chr19-15878779-G-C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001082.5(CYP4F2):​c.1555C>A​(p.Leu519Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0626 in 1,611,242 control chromosomes in the GnomAD database, including 1,872 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.078 (411 hom., cov: 32)
  • Exomes 𝑓: 0.061 (1461 hom.)
• Consequence: CYP4F2 NM_001082.5 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.84
• Publications: 26 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.001904577).
• BP6: Variant 19-15878779-G-T is Benign according to our data. Variant chr19-15878779-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3056325.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001082.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP4F2	NM_001082.5	MANE Select	c.1555C>A	p.Leu519Met	missense	Exon 13 of 13	NP_001073.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP4F2	ENST00000221700.11	TSL:1 MANE Select	c.1555C>A	p.Leu519Met	missense	Exon 13 of 13	ENSP00000221700.3	P78329-1
	CYP4F2	ENST00000011989.11	TSL:1	c.1555C>A	p.Leu519Met	missense	Exon 13 of 13	ENSP00000011989.8	A0A0A0MQR0
	CYP4F2	ENST00000886782.1		c.1651C>A	p.Leu551Met	missense	Exon 14 of 14	ENSP00000556841.1

Frequencies

GnomAD3 genomes AF: 0.0777 AC: 11771 AN: 151540 Hom.: 409 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0445

Gnomad ASJ AF: 0.0435

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0269

Gnomad FIN AF: 0.0781

Gnomad MID AF: 0.0573

Gnomad NFE AF: 0.0601

Gnomad OTH AF: 0.0557

GnomAD2 exomes AF: 0.0526 AC: 12982 AN: 246596 AF XY: 0.0509

Gnomad AFR exome AF: 0.140

Gnomad AMR exome AF: 0.0299

Gnomad ASJ exome AF: 0.0416

Gnomad EAS exome AF: 0.000164

Gnomad FIN exome AF: 0.0778

Gnomad NFE exome AF: 0.0580

Gnomad OTH exome AF: 0.0494

GnomAD4 exome AF: 0.0610 AC: 89089 AN: 1459586 Hom.: 1461 Cov.: 33 AF XY: 0.0601 AC XY: 43650 AN XY: 726136

African (AFR) AF: 0.143 AC: 4669 AN: 32682

American (AMR) AF: 0.0320 AC: 1427 AN: 44620

Ashkenazi Jewish (ASJ) AF: 0.0448 AC: 1167 AN: 26040

East Asian (EAS) AF: 0.000176 AC: 7 AN: 39676

South Asian (SAS) AF: 0.0341 AC: 2934 AN: 86124

European-Finnish (FIN) AF: 0.0778 AC: 4152 AN: 53338

Middle Eastern (MID) AF: 0.0368 AC: 212 AN: 5762

European-Non Finnish (NFE) AF: 0.0638 AC: 70902 AN: 1111072

Other (OTH) AF: 0.0600 AC: 3619 AN: 60272

GnomAD4 genome AF: 0.0777 AC: 11781 AN: 151656 Hom.: 411 Cov.: 32 AF XY: 0.0766 AC XY: 5683 AN XY: 74158

African (AFR) AF: 0.140 AC: 5741 AN: 41028

American (AMR) AF: 0.0444 AC: 679 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0435 AC: 151 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5168

South Asian (SAS) AF: 0.0269 AC: 130 AN: 4826

European-Finnish (FIN) AF: 0.0781 AC: 828 AN: 10602

Middle Eastern (MID) AF: 0.0616 AC: 18 AN: 292

European-Non Finnish (NFE) AF: 0.0601 AC: 4085 AN: 67970

Other (OTH) AF: 0.0551 AC: 116 AN: 2106

Alfa AF: 0.0573 Hom.: 152

ESP6500AA AF: 0.127 AC: 561

ESP6500EA AF: 0.0570 AC: 489

ExAC AF: 0.0544 AC: 6595

Asia WGS AF: 0.0200 AC: 70 AN: 3476

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	CYP4F2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.043
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.82	T
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Pathogenic	4.0	H
PhyloP100		1.8
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.22
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.96	D
Vest4		0.25
MPC		0.58
ClinPred		0.088	T
GERP RS		1.9
Varity_R		0.31
gMVP		0.66
Mutation Taster		=93/7	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: rs3093200; hg19: chr19-15989589; COSMIC: COSV55617569; COSMIC: COSV55617569;