rs3093105

Positions:

• chr19-15897578-A-C

Variant summary

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

The NM_001082.5(CYP4F2):​c.34T>G​(p.Trp12Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 1,613,268 control chromosomes in the GnomAD database, including 23,107 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.18 (2644 hom., cov: 31)
  • Exomes 𝑓: 0.16 (20463 hom.)
• Consequence: CYP4F2 NM_001082.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

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]

CYP4F2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0029075444).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP4F2	NM_001082.5	c.34T>G	p.Trp12Gly	missense_variant	2/13	ENST00000221700.11	NP_001073.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP4F2	ENST00000221700.11	c.34T>G	p.Trp12Gly	missense_variant	2/13	1	NM_001082.5	ENSP00000221700.3

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27248 AN: 151920 Hom.: 2632 Cov.: 31

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.0846

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.201

GnomAD3 exomes AF: 0.156 AC: 39015 AN: 250308 Hom.: 3482 AF XY: 0.159 AC XY: 21483 AN XY: 135416

Gnomad AFR exome AF: 0.236

Gnomad AMR exome AF: 0.108

Gnomad ASJ exome AF: 0.214

Gnomad EAS exome AF: 0.0881

Gnomad SAS exome AF: 0.166

Gnomad FIN exome AF: 0.114

Gnomad NFE exome AF: 0.169

Gnomad OTH exome AF: 0.173

GnomAD4 exome AF: 0.164 AC: 239014 AN: 1461230 Hom.: 20463 Cov.: 34 AF XY: 0.164 AC XY: 119310 AN XY: 726938

Gnomad4 AFR exome AF: 0.244

Gnomad4 AMR exome AF: 0.115

Gnomad4 ASJ exome AF: 0.211

Gnomad4 EAS exome AF: 0.107

Gnomad4 SAS exome AF: 0.164

Gnomad4 FIN exome AF: 0.113

Gnomad4 NFE exome AF: 0.166

Gnomad4 OTH exome AF: 0.168

GnomAD4 genome AF: 0.180 AC: 27291 AN: 152038 Hom.: 2644 Cov.: 31 AF XY: 0.178 AC XY: 13201 AN XY: 74322

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.164

Gnomad4 ASJ AF: 0.212

Gnomad4 EAS AF: 0.0854

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.202

Alfa AF: 0.175 Hom.: 865

Bravo AF: 0.185

TwinsUK AF: 0.172 AC: 636

ALSPAC AF: 0.173 AC: 668

ESP6500AA AF: 0.235 AC: 1034

ESP6500EA AF: 0.171 AC: 1468

ExAC AF: 0.160 AC: 19431

Asia WGS AF: 0.151 AC: 525 AN: 3478

EpiCase AF: 0.174

EpiControl AF: 0.181

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.036
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.81
DANN	Benign	0.32
DEOGEN2	Benign	0.037	T;.;.
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0014	N
LIST_S2	Benign	0.010	T;T;T
MetaRNN	Benign	0.0029	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-2.7	N;.;.
PrimateAI	Benign	0.41	T
PROVEAN	Benign	3.0	N;.;.
REVEL	Benign	0.18
Sift	Benign	1.0	T;.;.
Sift4G	Benign	0.38	T;T;.
Polyphen		0.0	B;.;.
Vest4		0.066
MPC		0.28
ClinPred		0.0054	T
GERP RS		-4.3
Varity_R		0.057
gMVP		0.23

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: rs3093105; hg19: chr19-16008388; COSMIC: COSV50000592; COSMIC: COSV50000592;