rs3093114

chr19-15895603-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001082.5(CYP4F2):c.246C>T(p.Ala82=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 1,592,672 control chromosomes in the GnomAD database, including 20,660 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (1829 hom., cov: 31)
  • Exomes 𝑓: 0.16 (18831 hom.)
• Consequence: CYP4F2 NM_001082.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.161

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

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 19-15895603-G-A is Benign according to our data. Variant chr19-15895603-G-A is described in ClinVar as [Benign]. Clinvar id is 3060160.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.161 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP4F2	NM_001082.5	c.246C>T	p.Ala82=	synonymous_variant	3/13	ENST00000221700.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP4F2	ENST00000221700.11	c.246C>T	p.Ala82=	synonymous_variant	3/13	1	NM_001082.5	P3

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22874 AN: 151860 Hom.: 1828 Cov.: 31

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.0934

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.0838

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.184

GnomAD3 exomes AF: 0.139 AC: 32138 AN: 231082 Hom.: 2580 AF XY: 0.144 AC XY: 18096 AN XY: 125380

Gnomad AFR exome AF: 0.126

Gnomad AMR exome AF: 0.0887

Gnomad ASJ exome AF: 0.192

Gnomad EAS exome AF: 0.0767

Gnomad SAS exome AF: 0.150

Gnomad FIN exome AF: 0.114

Gnomad NFE exome AF: 0.162

Gnomad OTH exome AF: 0.148

GnomAD4 exome AF: 0.158 AC: 228028 AN: 1440692 Hom.: 18831 Cov.: 32 AF XY: 0.159 AC XY: 113862 AN XY: 716214

Gnomad4 AFR exome AF: 0.134

Gnomad4 AMR exome AF: 0.0976

Gnomad4 ASJ exome AF: 0.197

Gnomad4 EAS exome AF: 0.104

Gnomad4 SAS exome AF: 0.153

Gnomad4 FIN exome AF: 0.113

Gnomad4 NFE exome AF: 0.165

Gnomad4 OTH exome AF: 0.156

GnomAD4 genome AF: 0.151 AC: 22892 AN: 151980 Hom.: 1829 Cov.: 31 AF XY: 0.150 AC XY: 11110 AN XY: 74308

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.0848

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.166

Gnomad4 OTH AF: 0.186

Alfa AF: 0.160 Hom.: 854

Bravo AF: 0.152

Asia WGS AF: 0.137 AC: 475 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

CYP4F2-related condition Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 15, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	8.6
Dann	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3093114; hg19: chr19-16006413; COSMIC: COSV50001262;