rs3093106

Variant names:

• chr19-15897447-T-C
• rs3093106
• NM_001082.5:c.165A>G
• CYP4F2 p.Pro55Pro

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001082.5(CYP4F2):​c.165A>G​(p.Pro55Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 1,613,120 control chromosomes in the GnomAD database, including 24,929 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.20 (3501 hom., cov: 31)
  • Exomes 𝑓: 0.17 (21428 hom.)
• Consequence: CYP4F2 NM_001082.5 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -5.94
• Publications: 28 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 19-15897447-T-C is Benign according to our data. Variant chr19-15897447-T-C is described in ClinVar as Benign. ClinVar VariationId is 3060298.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-5.94 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.303 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.165A>G	p.Pro55Pro	synonymous	Exon 2 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.165A>G	p.Pro55Pro	synonymous	Exon 2 of 13	ENSP00000221700.3	P78329-1
	CYP4F2	ENST00000011989.11	TSL:1	c.165A>G	p.Pro55Pro	synonymous	Exon 2 of 13	ENSP00000011989.8	A0A0A0MQR0
	CYP4F2	ENST00000886782.1		c.165A>G	p.Pro55Pro	synonymous	Exon 2 of 14	ENSP00000556841.1

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30465 AN: 151634 Hom.: 3489 Cov.: 31

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.0844

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.213

GnomAD2 exomes AF: 0.162 AC: 40744 AN: 250950 AF XY: 0.163

Gnomad AFR exome AF: 0.314

Gnomad AMR exome AF: 0.114

Gnomad ASJ exome AF: 0.218

Gnomad EAS exome AF: 0.0881

Gnomad FIN exome AF: 0.115

Gnomad NFE exome AF: 0.170

Gnomad OTH exome AF: 0.176

GnomAD4 exome AF: 0.166 AC: 242703 AN: 1461368 Hom.: 21428 Cov.: 33 AF XY: 0.166 AC XY: 120906 AN XY: 727016

African (AFR) AF: 0.323 AC: 10791 AN: 33424

American (AMR) AF: 0.121 AC: 5378 AN: 44616

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 5609 AN: 26104

East Asian (EAS) AF: 0.107 AC: 4253 AN: 39674

South Asian (SAS) AF: 0.164 AC: 14170 AN: 86230

European-Finnish (FIN) AF: 0.113 AC: 6036 AN: 53372

Middle Eastern (MID) AF: 0.199 AC: 1147 AN: 5756

European-Non Finnish (NFE) AF: 0.166 AC: 184871 AN: 1111834

Other (OTH) AF: 0.173 AC: 10448 AN: 60358

GnomAD4 genome AF: 0.201 AC: 30508 AN: 151752 Hom.: 3501 Cov.: 31 AF XY: 0.198 AC XY: 14708 AN XY: 74184

African (AFR) AF: 0.308 AC: 12706 AN: 41316

American (AMR) AF: 0.175 AC: 2674 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 743 AN: 3464

East Asian (EAS) AF: 0.0852 AC: 437 AN: 5132

South Asian (SAS) AF: 0.164 AC: 787 AN: 4796

European-Finnish (FIN) AF: 0.112 AC: 1185 AN: 10578

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.168 AC: 11392 AN: 67908

Other (OTH) AF: 0.214 AC: 449 AN: 2098

Alfa AF: 0.187 Hom.: 5321

Bravo AF: 0.210

Asia WGS AF: 0.155 AC: 538 AN: 3478

EpiCase AF: 0.174

EpiControl AF: 0.182

ClinVar

ClinVar submissions

Significance: 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
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.35
DANN	Benign	0.37
PhyloP100		-5.9
PromoterAI		-0.017	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3093106;

hg19: chr19-16008257;

COSMIC: COSV50000586;

COSMIC: COSV50000586;