Genetic Variant CYP4F2:p.Lys479Met (chr19-15878898-T-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001082.5(CYP4F2):c.1436A>T(p.Lys479Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000465 in 1,614,028 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

CYP4F2
NM_001082.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.63

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 -4 ACMG points.

BS2

High AC in GnomAd4 at 40 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP4F2	NM_001082.5 link	c.1436A>T	p.Lys479Met	missense_variant	Exon 13 of 13	ENST00000221700.11	NP_001073.3	P78329-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CYP4F2	ENST00000221700.11 link	c.1436A>T	p.Lys479Met	missense_variant	Exon 13 of 13	1	NM_001082.5	ENSP00000221700.3	P78329-1
CYP4F2	ENST00000011989.11 link	c.1436A>T	p.Lys479Met	missense_variant	Exon 13 of 13	1		ENSP00000011989.8	A0A0A0MQR0
CYP4F2	ENST00000589654.2 link	c.*1A>T		3_prime_UTR_variant	Exon 3 of 3	3		ENSP00000467846.1	K7EQI8
CYP4F2	ENST00000392846.7 link	n.1379A>T		non_coding_transcript_exon_variant	Exon 11 of 11	2

Frequencies

GnomAD3 genomes

AF:

0.000256

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000916

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000318

AC:

AN:

251258

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135798

show subpopulations

Gnomad AFR exome

AF:

0.000493

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000239

AC:

AN:

1461716

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727154

show subpopulations

Gnomad4 AFR exome

AF:

0.000836

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.000263

AC:

AN:

152312

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000938

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000227

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000412

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.65

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.28

T;.

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.80

T;T

M_CAP

Benign

0.039

MetaRNN

Uncertain

0.48

T;T

MetaSVM

Uncertain

0.27

MutationAssessor

Pathogenic

4.5

H;.

PrimateAI

Uncertain

0.66

PROVEAN

Pathogenic

-5.1

D;.

REVEL

Uncertain

0.60

Sift

Uncertain

0.0040

D;.

Sift4G

Uncertain

0.0070

D;D

Polyphen

0.97

D;.

Vest4

0.47

MVP

0.87

MPC

0.74

ClinPred

0.75

GERP RS

2.6

Varity_R

0.56

gMVP

0.90

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over