Variant chr19-15886018-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001082.5(CYP4F2):c.1021C>G(p.Leu341Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00743 in 1,614,066 control chromosomes in the GnomAD database, including 73 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0044 ( 2 hom., cov: 31)

Exomes 𝑓: 0.0077 ( 71 hom. )

Consequence

CYP4F2
NM_001082.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.45

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.018367171).

BP6

Variant 19-15886018-G-C is Benign according to our data. Variant chr19-15886018-G-C is described in ClinVar as [Benign]. Clinvar id is 771928.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.00775 (11323/1461812) while in subpopulation SAS AF= 0.0186 (1601/86254). AF 95% confidence interval is 0.0178. There are 71 homozygotes in gnomad4_exome. There are 5817 alleles in male gnomad4_exome subpopulation. Median coverage is 36. This position pass quality control queck.

BS2

High AC in GnomAd4 at 669 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP4F2	NM_001082.5 linkuse as main transcript	c.1021C>G	p.Leu341Val	missense_variant	9/13	ENST00000221700.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP4F2	ENST00000221700.11 linkuse as main transcript	c.1021C>G	p.Leu341Val	missense_variant	9/13	1	NM_001082.5	P3	P78329-1

Frequencies

GnomAD3 genomes

AF:

0.00439

AC:

668

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00150

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0166

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00689

Gnomad OTH

AF:

0.00479

GnomAD3 exomes

AF:

0.00577

AC:

1450

AN:

251322

Hom.:

AF XY:

0.00633

AC XY:

860

AN XY:

135804

show subpopulations

Gnomad AFR exome

AF:

0.00135

Gnomad AMR exome

AF:

0.00211

Gnomad ASJ exome

AF:

0.00427

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0168

Gnomad FIN exome

AF:

0.000416

Gnomad NFE exome

AF:

0.00669

Gnomad OTH exome

AF:

0.00457

GnomAD4 exome

AF:

0.00775

AC:

11323

AN:

1461812

Hom.:

Cov.:

AF XY:

0.00800

AC XY:

5817

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.00102

Gnomad4 AMR exome

AF:

0.00212

Gnomad4 ASJ exome

AF:

0.00475

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0186

Gnomad4 FIN exome

AF:

0.000674

Gnomad4 NFE exome

AF:

0.00805

Gnomad4 OTH exome

AF:

0.00717

GnomAD4 genome

AF:

0.00439

AC:

669

AN:

152254

Hom.:

Cov.:

AF XY:

0.00408

AC XY:

304

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.00144

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0168

Gnomad4 FIN

AF:

0.000753

Gnomad4 NFE

AF:

0.00689

Gnomad4 OTH

AF:

0.00474

Alfa

AF:

0.00572

Hom.:

Bravo

AF:

0.00413

TwinsUK

AF:

0.00782

AC:

ALSPAC

AF:

0.00701

AC:

ESP6500AA

AF:

0.00250

AC:

ESP6500EA

AF:

0.00779

AC:

ExAC

AF:

0.00624

AC:

758

EpiCase

AF:

0.00720

EpiControl

AF:

0.00735

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

T;.

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.86

LIST_S2

Pathogenic

0.98

D;D

MetaRNN

Benign

0.018

T;T

MetaSVM

Uncertain

0.37

MutationAssessor

Uncertain

2.8

M;.

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-2.7

D;.

REVEL

Pathogenic

0.70

Sift

Uncertain

0.0020

D;.

Sift4G

Uncertain

0.0040

D;D

Polyphen

1.0

D;.

Vest4

0.70

MVP

0.84

MPC

0.56

ClinPred

0.017

GERP RS

2.6

Varity_R

0.68

gMVP

0.45

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