19-15886018-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.45

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 Benign. Variant got -14 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_single_submitter, 1 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 GnomAd at 668 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP4F2	NM_001082.5	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	c.1021C>G	p.Leu341Val	missense_variant	9/13	1	NM_001082.5	P3

Frequencies

GnomAD3 genomes AF: 0.00439 AC: 668 AN: 152136 Hom.: 2 Cov.: 31

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.: 10 AF XY: 0.00633 AC XY: 860 AN XY: 135804

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.: 71 Cov.: 36 AF XY: 0.00800 AC XY: 5817 AN XY: 727224

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.: 2 Cov.: 31 AF XY: 0.00408 AC XY: 304 AN XY: 74438

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.: 3

Bravo AF: 0.00413

TwinsUK AF: 0.00782 AC: 29

ALSPAC AF: 0.00701 AC: 27

ESP6500AA AF: 0.00250 AC: 11

ESP6500EA AF: 0.00779 AC: 67

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

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	T
BayesDel_noAF	Benign	-0.12
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Benign	0.23	T;.
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Pathogenic	0.98	D;D
MetaRNN	Benign	0.018	T;T
MetaSVM	Uncertain	0.37	D
MutationAssessor	Uncertain	2.8	M;.
MutationTaster	Benign	0.99	D;D;D
PrimateAI	Benign	0.48	T
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	T
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

Other links and lift over

dbSNP: rs145174239; hg19: chr19-15996828; COSMIC: COSV105001584;