Variant 19-15878845-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001082.5(CYP4F2):c.1489G>A(p.Glu497Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CYP4F2
NM_001082.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.275

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09211877).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP4F2	NM_001082.5 linkuse as main transcript	c.1489G>A	p.Glu497Lys	missense_variant	13/13	ENST00000221700.11	NP_001073.3	P78329-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CYP4F2	ENST00000221700.11 linkuse as main transcript	c.1489G>A	p.Glu497Lys	missense_variant	13/13	1	NM_001082.5	ENSP00000221700.3	P78329-1
CYP4F2	ENST00000011989.11 linkuse as main transcript	c.1489G>A	p.Glu497Lys	missense_variant	13/13	1		ENSP00000011989.8	A0A0A0MQR0
CYP4F2	ENST00000589654.2 linkuse as main transcript	c.*54G>A		3_prime_UTR_variant	3/3	3		ENSP00000467846.1	K7EQI8
CYP4F2	ENST00000392846.7 linkuse as main transcript	n.1432G>A		non_coding_transcript_exon_variant	11/11	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250644

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135602

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000137

AC:

AN:

1461704

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 14, 2024

The c.1489G>A (p.E497K) alteration is located in exon 13 (coding exon 12) of the CYP4F2 gene. This alteration results from a G to A substitution at nucleotide position 1489, causing the glutamic acid (E) at amino acid position 497 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.049

T;.

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.013

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.0062

MetaRNN

Benign

0.092

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.2

M;.

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.6

N;.

REVEL

Benign

0.10

Sift

Benign

0.45

T;.

Sift4G

Benign

0.71

T;T

Polyphen

0.016

B;.

Vest4

0.054

MutPred

0.44

Gain of MoRF binding (P = 0.0082);Gain of MoRF binding (P = 0.0082);

MVP

0.54

MPC

0.28

ClinPred

0.055

GERP RS

1.4

Varity_R

0.16

gMVP

0.83

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