chr19-15879401-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001082.5(CYP4F2):​c.1342G>A​(p.Glu448Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000102 in 1,460,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00010 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

CYP4F2
NM_001082.5 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.921
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.07914406).
BS2
High AC in GnomAdExome4 at 149 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CYP4F2NM_001082.5 linkuse as main transcriptc.1342G>A p.Glu448Lys missense_variant 12/13 ENST00000221700.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CYP4F2ENST00000221700.11 linkuse as main transcriptc.1342G>A p.Glu448Lys missense_variant 12/131 NM_001082.5 P3P78329-1
CYP4F2ENST00000011989.11 linkuse as main transcriptc.1342G>A p.Glu448Lys missense_variant 12/131 A1
CYP4F2ENST00000589654.2 linkuse as main transcriptc.132G>A p.Gln44= synonymous_variant 2/33
CYP4F2ENST00000392846.7 linkuse as main transcriptn.1285G>A non_coding_transcript_exon_variant 10/112

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
17
AN:
151958
Hom.:
0
Cov.:
32
FAILED QC
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000415
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000191
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000278
AC:
7
AN:
251350
Hom.:
0
AF XY:
0.0000368
AC XY:
5
AN XY:
135836
show subpopulations
Gnomad AFR exome
AF:
0.00
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:
0.0000462
Gnomad NFE exome
AF:
0.0000528
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000102
AC:
149
AN:
1460218
Hom.:
0
Cov.:
33
AF XY:
0.000102
AC XY:
74
AN XY:
726352
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000616
Gnomad4 FIN exome
AF:
0.0000562
Gnomad4 NFE exome
AF:
0.0000756
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.000112
AC:
17
AN:
152076
Hom.:
0
Cov.:
32
AF XY:
0.0000807
AC XY:
6
AN XY:
74356
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000415
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000192
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000144
Hom.:
0
ExAC
AF:
0.000198
AC:
24

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 submitterclinical testingAmbry GeneticsMar 25, 2024The c.1342G>A (p.E448K) alteration is located in exon 12 (coding exon 11) of the CYP4F2 gene. This alteration results from a G to A substitution at nucleotide position 1342, causing the glutamic acid (E) at amino acid position 448 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
0.073
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
17
DANN
Uncertain
0.99
DEOGEN2
Benign
0.12
T;.
Eigen
Benign
-0.66
Eigen_PC
Benign
-0.77
FATHMM_MKL
Benign
0.050
N
LIST_S2
Benign
0.57
T;T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.079
T;T
MetaSVM
Benign
-0.68
T
MutationAssessor
Uncertain
2.8
M;.
MutationTaster
Benign
1.0
N;N
PrimateAI
Uncertain
0.51
T
PROVEAN
Uncertain
-2.4
N;.
REVEL
Benign
0.15
Sift
Uncertain
0.029
D;.
Sift4G
Uncertain
0.034
D;D
Polyphen
0.0010
B;.
Vest4
0.23
MVP
0.63
MPC
0.26
ClinPred
0.10
T
GERP RS
0.75
Varity_R
0.32
gMVP
0.76

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.

Other links and lift over

dbSNP: rs764508037; hg19: chr19-15990211; API