dbSNP rs3093114: CYP4F2:p.Ala82Ala (chr19-15895603-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

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

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.161

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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 link	c.246C>T	p.Ala82Ala	synonymous_variant	Exon 3 of 13	ENST00000221700.11	NP_001073.3	P78329-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP4F2	ENST00000221700.11 link	c.246C>T	p.Ala82Ala	synonymous_variant	Exon 3 of 13	1	NM_001082.5	ENSP00000221700.3		P78329-1

Frequencies

GnomAD3 genomes

AF:

0.151

AC:

22874

AN:

151860

Hom.:

1828

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.159

AC XY:

113862

AN XY:

716214

show subpopulations

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.:

AF XY:

0.150

AC XY:

11110

AN XY:

74308

show subpopulations

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: no assertion criteria provided

LINK: link

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over