Variant 19-15878779-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001082.5(CYP4F2):c.1555C>A(p.Leu519Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0626 in 1,611,242 control chromosomes in the GnomAD database, including 1,872 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.078 ( 411 hom., cov: 32)

Exomes 𝑓: 0.061 ( 1461 hom. )

Consequence

CYP4F2
NM_001082.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.84

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 (MetaRNN=0.001904577).

BP6

Variant 19-15878779-G-T is Benign according to our data. Variant chr19-15878779-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3056325.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP4F2	NM_001082.5 linkuse as main transcript	c.1555C>A	p.Leu519Met	missense_variant	13/13	ENST00000221700.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP4F2	ENST00000221700.11 linkuse as main transcript	c.1555C>A	p.Leu519Met	missense_variant	13/13	1	NM_001082.5	P3	P78329-1
CYP4F2	ENST00000011989.11 linkuse as main transcript	c.1555C>A	p.Leu519Met	missense_variant	13/13	1		A1
CYP4F2	ENST00000589654.2 linkuse as main transcript	c.*120C>A		3_prime_UTR_variant	3/3	3
CYP4F2	ENST00000392846.7 linkuse as main transcript	n.1498C>A		non_coding_transcript_exon_variant	11/11	2

Frequencies

GnomAD3 genomes

AF:

0.0777

AC:

11771

AN:

151540

Hom.:

409

Cov.:

show subpopulations

Gnomad AFR

AF:

0.140

Gnomad AMI

AF:

0.0351

Gnomad AMR

AF:

0.0445

Gnomad ASJ

AF:

0.0435

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0269

Gnomad FIN

AF:

0.0781

Gnomad MID

AF:

0.0573

Gnomad NFE

AF:

0.0601

Gnomad OTH

AF:

0.0557

GnomAD3 exomes

AF:

0.0526

AC:

12982

AN:

246596

Hom.:

287

AF XY:

0.0509

AC XY:

6814

AN XY:

133800

show subpopulations

Gnomad AFR exome

AF:

0.140

Gnomad AMR exome

AF:

0.0299

Gnomad ASJ exome

AF:

0.0416

Gnomad EAS exome

AF:

0.000164

Gnomad SAS exome

AF:

0.0330

Gnomad FIN exome

AF:

0.0778

Gnomad NFE exome

AF:

0.0580

Gnomad OTH exome

AF:

0.0494

GnomAD4 exome

AF:

0.0610

AC:

89089

AN:

1459586

Hom.:

1461

Cov.:

AF XY:

0.0601

AC XY:

43650

AN XY:

726136

show subpopulations

Gnomad4 AFR exome

AF:

0.143

Gnomad4 AMR exome

AF:

0.0320

Gnomad4 ASJ exome

AF:

0.0448

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.0341

Gnomad4 FIN exome

AF:

0.0778

Gnomad4 NFE exome

AF:

0.0638

Gnomad4 OTH exome

AF:

0.0600

GnomAD4 genome

AF:

0.0777

AC:

11781

AN:

151656

Hom.:

411

Cov.:

AF XY:

0.0766

AC XY:

5683

AN XY:

74158

show subpopulations

Gnomad4 AFR

AF:

0.140

Gnomad4 AMR

AF:

0.0444

Gnomad4 ASJ

AF:

0.0435

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0269

Gnomad4 FIN

AF:

0.0781

Gnomad4 NFE

AF:

0.0601

Gnomad4 OTH

AF:

0.0551

Alfa

AF:

0.0507

Hom.:

ESP6500AA

AF:

0.127

AC:

561

ESP6500EA

AF:

0.0570

AC:

489

ExAC

AF:

0.0544

AC:

6595

Asia WGS

AF:

0.0200

AC:

AN:

3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CYP4F2-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 05, 2023

This variant is classified as likely 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

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

T;.

Eigen

Benign

0.16

Eigen_PC

Benign

0.043

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.82

T;T

MetaRNN

Benign

0.0019

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Pathogenic

4.0

H;.

MutationTaster

Benign

0.20

P;P

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.6

N;.

REVEL

Benign

0.22

Sift

Uncertain

0.0020

D;.

Sift4G

Uncertain

0.0040

D;D

Polyphen

0.96

D;.

Vest4

0.25

MPC

0.58

ClinPred

0.088

GERP RS

1.9

Varity_R

0.31

gMVP

0.66

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

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