Variant chr19-15878920-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_001082.5(CYP4F2):c.1414A>G(p.Thr472Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.17 ( 4 hom. )

Failed GnomAD Quality Control

Consequence

CYP4F2
NM_001082.5 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.149

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 Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011447012).

BP6

Variant 19-15878920-T-C is Benign according to our data. Variant chr19-15878920-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3059292.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP4F2	NM_001082.5 linkuse as main transcript	c.1414A>G	p.Thr472Ala	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.1414A>G	p.Thr472Ala	missense_variant	13/13	1	NM_001082.5	P3	P78329-1
CYP4F2	ENST00000011989.11 linkuse as main transcript	c.1414A>G	p.Thr472Ala	missense_variant	13/13	1		A1
CYP4F2	ENST00000589654.2 linkuse as main transcript	c.204A>G	p.Arg68=	synonymous_variant	3/3	3
CYP4F2	ENST00000392846.7 linkuse as main transcript	n.1357A>G		non_coding_transcript_exon_variant	11/11	2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

3416

AN:

103230

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0466

Gnomad AMI

AF:

0.0144

Gnomad AMR

AF:

0.0374

Gnomad ASJ

AF:

0.0170

Gnomad EAS

AF:

0.0373

Gnomad SAS

AF:

0.0160

Gnomad FIN

AF:

0.0506

Gnomad MID

AF:

0.0159

Gnomad NFE

AF:

0.0246

Gnomad OTH

AF:

0.0303

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.167

AC:

147828

AN:

887088

Hom.:

Cov.:

AF XY:

0.157

AC XY:

70028

AN XY:

444656

show subpopulations

Gnomad4 AFR exome

AF:

0.229

Gnomad4 AMR exome

AF:

0.176

Gnomad4 ASJ exome

AF:

0.0820

Gnomad4 EAS exome

AF:

0.0885

Gnomad4 SAS exome

AF:

0.0638

Gnomad4 FIN exome

AF:

0.136

Gnomad4 NFE exome

AF:

0.183

Gnomad4 OTH exome

AF:

0.133

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0331

AC:

3419

AN:

103298

Hom.:

Cov.:

AF XY:

0.0383

AC XY:

1904

AN XY:

49714

show subpopulations

Gnomad4 AFR

AF:

0.0465

Gnomad4 AMR

AF:

0.0375

Gnomad4 ASJ

AF:

0.0170

Gnomad4 EAS

AF:

0.0374

Gnomad4 SAS

AF:

0.0161

Gnomad4 FIN

AF:

0.0506

Gnomad4 NFE

AF:

0.0246

Gnomad4 OTH

AF:

0.0300

Alfa

AF:

0.165

Hom.:

ExAC

AF:

0.349

AC:

42415

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CYP4F2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

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

0.070

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.30

DANN

Benign

0.35

DEOGEN2

Benign

0.052

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.25

T;T

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

L;.

MutationTaster

Benign

0.97

N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-2.1

N;.

REVEL

Benign

0.12

Sift

Benign

0.41

T;.

Sift4G

Benign

0.33

T;T

Polyphen

0.0

B;.

Vest4

0.030

MPC

0.15

ClinPred

0.0020

GERP RS

0.20

Varity_R

0.058

gMVP

0.56

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