rs3093105

Variant names:

• chr19-15897578-A-C
• rs3093105
• NM_001082.5:c.34T>G

Variant summary

Our verdict is Benign. The variant received -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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 71 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 (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 rank	MANE	Protein	UniProt
CYP4F2	NM_001082.5	c.34T>G	p.Trp12Gly	missense_variant	Exon 2 of 13	ENST00000221700.11	NP_001073.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP4F2	ENST00000221700.11	c.34T>G	p.Trp12Gly	missense_variant	Exon 2 of 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

GnomAD2 exomes AF: 0.156 AC: 39015 AN: 250308 AF XY: 0.159

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 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

African (AFR) AF: 0.244 AC: 8146 AN: 33426

American (AMR) AF: 0.115 AC: 5118 AN: 44618

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 5510 AN: 26094

East Asian (EAS) AF: 0.107 AC: 4249 AN: 39674

South Asian (SAS) AF: 0.164 AC: 14144 AN: 86204

European-Finnish (FIN) AF: 0.113 AC: 6018 AN: 53348

Middle Eastern (MID) AF: 0.195 AC: 1121 AN: 5760

European-Non Finnish (NFE) AF: 0.166 AC: 184593 AN: 1111746

Other (OTH) AF: 0.168 AC: 10115 AN: 60360

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

African (AFR) AF: 0.234 AC: 9694 AN: 41464

American (AMR) AF: 0.164 AC: 2511 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 737 AN: 3470

East Asian (EAS) AF: 0.0854 AC: 439 AN: 5140

South Asian (SAS) AF: 0.164 AC: 787 AN: 4812

European-Finnish (FIN) AF: 0.112 AC: 1185 AN: 10604

Middle Eastern (MID) AF: 0.164 AC: 48 AN: 292

European-Non Finnish (NFE) AF: 0.167 AC: 11379 AN: 67948

Other (OTH) AF: 0.202 AC: 426 AN: 2104

Alfa AF: 0.174 Hom.: 1283

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;.;.
PhyloP100		-1.3
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
PromoterAI		0.021	Neutral
Varity_R		0.057
gMVP		0.23
Mutation Taster		=300/0	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: rs3093105; hg19: chr19-16008388; COSMIC: COSV50000592; COSMIC: COSV50000592;