19-15878832-T-C

Position:

• chr19-15878832-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001082.5(CYP4F2):​c.1502A>G​(p.Lys501Arg) 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. 12/21 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)
• Consequence: CYP4F2 NM_001082.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.791

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2681265).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP4F2	NM_001082.5	c.1502A>G	p.Lys501Arg	missense_variant	13/13	ENST00000221700.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP4F2	ENST00000221700.11	c.1502A>G	p.Lys501Arg	missense_variant	13/13	1	NM_001082.5	P3
CYP4F2	ENST00000011989.11	c.1502A>G	p.Lys501Arg	missense_variant	13/13	1		A1
CYP4F2	ENST00000589654.2	c.*67A>G		3_prime_UTR_variant	3/3	3
CYP4F2	ENST00000392846.7	n.1445A>G		non_coding_transcript_exon_variant	11/11	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 06, 2022

The c.1502A>G (p.K501R) alteration is located in exon 13 (coding exon 12) of the CYP4F2 gene. This alteration results from a A to G substitution at nucleotide position 1502, causing the lysine (K) at amino acid position 501 to be replaced by an arginine (R). 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	0.098
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.052	T;.
Eigen	Benign	0.18
Eigen_PC	Benign	0.069
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.84	T;T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.27	T;T
MetaSVM	Benign	-0.52	T
MutationAssessor	Uncertain	2.8	M;.
MutationTaster	Benign	0.99	N;N
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-2.5	N;.
REVEL	Benign	0.15
Sift	Benign	0.14	T;.
Sift4G	Benign	0.54	T;T
Polyphen		0.97	D;.
Vest4		0.16
MutPred		0.36		Loss of ubiquitination at K501 (P = 0.0148);Loss of ubiquitination at K501 (P = 0.0148);
MVP		0.80
MPC		0.16
ClinPred		0.73	D
GERP RS		2.6
Varity_R		0.18
gMVP		0.60

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

Other links and lift over

dbSNP: rs2089322394; hg19: chr19-15989642;