19-15879621-C-T

Position:

chr19-15879621-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_StrongBA1

The NM_001082.5(CYP4F2):c.1297G>A(p.Val433Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 1,613,898 control chromosomes in the GnomAD database, including 69,909 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as drug response (★★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.23 ( 4700 hom., cov: 31)

Exomes 𝑓: 0.29 ( 65209 hom. )

Consequence

CYP4F2
NM_001082.5 missense

Scores

Clinical Significance

drug response reviewed by expert panel B:2O:2

Conservation

PhyloP100: 1.68

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:

CYP4F2 (HGNC:):

CYP4F2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009836018).

BP6

Variant 19-15879621-C-T is Benign according to our data. Variant chr19-15879621-C-T is described in ClinVar as [drug_response]. Clinvar id is 225969.Status of the report is reviewed_by_expert_panel, 3 stars. We mark this variant Likely_benign, oryginal submissions are: {Benign=1, drug_response=2}.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP4F2	NM_001082.5 linkuse as main transcript	c.1297G>A	p.Val433Met	missense_variant	11/13	ENST00000221700.11	NP_001073.3	P78329-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP4F2	ENST00000221700.11 linkuse as main transcript	c.1297G>A	p.Val433Met	missense_variant	11/13	1	NM_001082.5	ENSP00000221700.3		P78329-1

Frequencies

GnomAD3 genomes

AF:

0.230

AC:

34923

AN:

151950

Hom.:

4697

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0991

Gnomad AMI

AF:

0.202

Gnomad AMR

AF:

0.258

Gnomad ASJ

AF:

0.347

Gnomad EAS

AF:

0.245

Gnomad SAS

AF:

0.402

Gnomad FIN

AF:

0.199

Gnomad MID

AF:

0.396

Gnomad NFE

AF:

0.286

Gnomad OTH

AF:

0.291

GnomAD3 exomes

AF:

0.273

AC:

68663

AN:

251380

Hom.:

10436

AF XY:

0.286

AC XY:

38866

AN XY:

135850

show subpopulations

Gnomad AFR exome

AF:

0.0966

Gnomad AMR exome

AF:

0.229

Gnomad ASJ exome

AF:

0.345

Gnomad EAS exome

AF:

0.249

Gnomad SAS exome

AF:

0.398

Gnomad FIN exome

AF:

0.197

Gnomad NFE exome

AF:

0.289

Gnomad OTH exome

AF:

0.295

GnomAD4 exome

AF:

0.294

AC:

429090

AN:

1461830

Hom.:

65209

Cov.:

AF XY:

0.298

AC XY:

216369

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.0961

Gnomad4 AMR exome

AF:

0.229

Gnomad4 ASJ exome

AF:

0.348

Gnomad4 EAS exome

AF:

0.269

Gnomad4 SAS exome

AF:

0.390

Gnomad4 FIN exome

AF:

0.196

Gnomad4 NFE exome

AF:

0.298

Gnomad4 OTH exome

AF:

0.294

GnomAD4 genome

AF:

0.230

AC:

34933

AN:

152068

Hom.:

4700

Cov.:

AF XY:

0.230

AC XY:

17063

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.0990

Gnomad4 AMR

AF:

0.258

Gnomad4 ASJ

AF:

0.347

Gnomad4 EAS

AF:

0.246

Gnomad4 SAS

AF:

0.401

Gnomad4 FIN

AF:

0.199

Gnomad4 NFE

AF:

0.286

Gnomad4 OTH

AF:

0.294

Alfa

AF:

0.283

Hom.:

16272

Bravo

AF:

0.226

TwinsUK

AF:

0.308

AC:

1143

ALSPAC

AF:

0.301

AC:

1160

ESP6500AA

AF:

0.0971

AC:

428

ESP6500EA

AF:

0.291

AC:

2504

ExAC

AF:

0.272

AC:

33078

Asia WGS

AF:

0.332

AC:

1154

AN:

3478

EpiCase

AF:

0.300

EpiControl

AF:

0.309

ClinVar

Significance: drug response

Submissions summary: Benign:2Other:2

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

CYP4F2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 22, 2021

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). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 12, 2023

- -

warfarin response - Dosage

Other:1

drug response, reviewed by expert panel

curation

PharmGKB

Mar 24, 2021

PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or an FDA-approved drug label annotation. Annotations of drug labels or clinical guidelines must give prescribing guidance for specific variants (e.g. CYP2C9*3, HLA-B*57:01) or provide mapping from defined allele functions to diplotypes and phenotypes to be used as supporting evidence for a level 1A clinical annotation. Level 1A clinical annotations must also be supported by at least one publication in addition to a clinical guideline or drug label with variant-specific prescribing guidance. Drug-variant association: Dosage

acenocoumarol response - Dosage

Other:1

drug response, reviewed by expert panel

curation

PharmGKB

Mar 24, 2021

PharmGKB Level of Evidence 2A: Variants in Level 2A clinical annotations are found in PharmGKB’s Tier 1 Very Important Pharmacogenes (VIPs). These variants are in known pharmacogenes, implying causation of drug phenotype is more likely. These clinical annotations describe variant-drug combinations with a moderate level of evidence supporting the association. For example, the association may be found in multiple cohorts, but there may be a minority of studies that do not support the majority assertion. Level 2A clinical annotations must be supported by at least two independent publications. Drug-variant association: Dosage

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

T;.

Eigen

Uncertain

0.33

Eigen_PC

Benign

0.13

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.80

T;T

MetaRNN

Benign

0.0098

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

4.0

H;.

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-2.7

D;.

REVEL

Uncertain

0.30

Sift

Uncertain

0.0050

D;.

Sift4G

Pathogenic

0.0010

D;D

Polyphen

1.0

D;.

Vest4

0.14

MPC

0.64

ClinPred

0.050

GERP RS

1.7

Varity_R

0.65

gMVP

0.81

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