rs3093114

Variant names:

• chr19-15895603-G-A
• rs3093114
• NM_001082.5:c.246C>T

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.246C>T​(p.Ala82Ala) 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 (no stars).

• Frequency:
  • Genomes: 𝑓 0.15 (1829 hom., cov: 31)
  • Exomes 𝑓: 0.16 (18831 hom.)
• Consequence: CYP4F2 NM_001082.5 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.161
• Publications: 17 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=-0.84).
• BP6: Variant 19-15895603-G-A is Benign according to our data. Variant chr19-15895603-G-A is described in ClinVar as Benign. ClinVar VariationId is 3060160.Status of the report is no_assertion_criteria_provided, 0 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 rank	MANE	Protein	UniProt
CYP4F2	NM_001082.5	c.246C>T	p.Ala82Ala	synonymous_variant	Exon 3 of 13	ENST00000221700.11	NP_001073.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP4F2	ENST00000221700.11	c.246C>T	p.Ala82Ala	synonymous_variant	Exon 3 of 13	1	NM_001082.5	ENSP00000221700.3

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

GnomAD2 exomes AF: 0.139 AC: 32138 AN: 231082 AF XY: 0.144

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 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

African (AFR) AF: 0.134 AC: 4280 AN: 32042

American (AMR) AF: 0.0976 AC: 4014 AN: 41130

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 5034 AN: 25578

East Asian (EAS) AF: 0.104 AC: 3925 AN: 37596

South Asian (SAS) AF: 0.153 AC: 12658 AN: 82754

European-Finnish (FIN) AF: 0.113 AC: 6019 AN: 53260

Middle Eastern (MID) AF: 0.181 AC: 1036 AN: 5714

European-Non Finnish (NFE) AF: 0.165 AC: 181774 AN: 1103094

Other (OTH) AF: 0.156 AC: 9288 AN: 59524

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

African (AFR) AF: 0.136 AC: 5635 AN: 41428

American (AMR) AF: 0.154 AC: 2355 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 690 AN: 3462

East Asian (EAS) AF: 0.0848 AC: 438 AN: 5166

South Asian (SAS) AF: 0.158 AC: 760 AN: 4818

European-Finnish (FIN) AF: 0.112 AC: 1184 AN: 10582

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.166 AC: 11309 AN: 67936

Other (OTH) AF: 0.186 AC: 391 AN: 2104

Alfa AF: 0.159 Hom.: 868

Bravo AF: 0.152

Asia WGS AF: 0.137 AC: 475 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

CYP4F2-related disorder Benign:1

Nov 15, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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
PhyloP100		0.16
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3093114; hg19: chr19-16006413; COSMIC: COSV50001262;