rs3093153

chr19-15890405-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001082.5(CYP4F2):c.554G>T(p.Gly185Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0484 in 1,613,994 control chromosomes in the GnomAD database, including 2,286 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.049 (199 hom., cov: 32)
  • Exomes 𝑓: 0.048 (2087 hom.)
• Consequence: CYP4F2 NM_001082.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.75

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=0.0025855303).
• BP6: Variant 19-15890405-C-A is Benign according to our data. Variant chr19-15890405-C-A is described in ClinVar as [Benign]. Clinvar id is 3055377.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP4F2	NM_001082.5	c.554G>T	p.Gly185Val	missense_variant	6/13	ENST00000221700.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP4F2	ENST00000221700.11	c.554G>T	p.Gly185Val	missense_variant	6/13	1	NM_001082.5	P3
CYP4F2	ENST00000011989.11	c.554G>T	p.Gly185Val	missense_variant	6/13	1		A1
CYP4F2	ENST00000392846.7	n.497G>T		non_coding_transcript_exon_variant	4/11	2
CYP4F2	ENST00000587671.2	c.*139G>T		3_prime_UTR_variant, NMD_transcript_variant	5/8	5

Frequencies

GnomAD3 genomes AF: 0.0490 AC: 7452 AN: 152142 Hom.: 197 Cov.: 32

Gnomad AFR AF: 0.0332

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.0408

Gnomad ASJ AF: 0.0404

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00455

Gnomad FIN AF: 0.0980

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0599

Gnomad OTH AF: 0.0482

GnomAD3 exomes AF: 0.0461 AC: 11595 AN: 251462 Hom.: 380 AF XY: 0.0458 AC XY: 6218 AN XY: 135902

Gnomad AFR exome AF: 0.0328

Gnomad AMR exome AF: 0.0277

Gnomad ASJ exome AF: 0.0437

Gnomad EAS exome AF: 0.000326

Gnomad SAS exome AF: 0.00679

Gnomad FIN exome AF: 0.0975

Gnomad NFE exome AF: 0.0616

Gnomad OTH exome AF: 0.0535

GnomAD4 exome AF: 0.0483 AC: 70591 AN: 1461734 Hom.: 2087 Cov.: 31 AF XY: 0.0477 AC XY: 34684 AN XY: 727178

Gnomad4 AFR exome AF: 0.0308

Gnomad4 AMR exome AF: 0.0290

Gnomad4 ASJ exome AF: 0.0413

Gnomad4 EAS exome AF: 0.000227

Gnomad4 SAS exome AF: 0.00759

Gnomad4 FIN exome AF: 0.100

Gnomad4 NFE exome AF: 0.0526

Gnomad4 OTH exome AF: 0.0421

GnomAD4 genome AF: 0.0490 AC: 7467 AN: 152260 Hom.: 199 Cov.: 32 AF XY: 0.0488 AC XY: 3630 AN XY: 74458

Gnomad4 AFR AF: 0.0335

Gnomad4 AMR AF: 0.0408

Gnomad4 ASJ AF: 0.0404

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00477

Gnomad4 FIN AF: 0.0980

Gnomad4 NFE AF: 0.0599

Gnomad4 OTH AF: 0.0473

Alfa AF: 0.0552 Hom.: 433

Bravo AF: 0.0449

TwinsUK AF: 0.0553 AC: 205

ALSPAC AF: 0.0493 AC: 190

ESP6500AA AF: 0.0297 AC: 131

ESP6500EA AF: 0.0594 AC: 511

ExAC AF: 0.0471 AC: 5723

Asia WGS AF: 0.00982 AC: 34 AN: 3478

EpiCase AF: 0.0601

EpiControl AF: 0.0583

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

CYP4F2-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 06, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.24
Cadd	Benign	18
Dann	Uncertain	0.98
DEOGEN2	Benign	0.26	T;.
Eigen	Benign	0.027
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.55	D
LIST_S2	Uncertain	0.95	D;D
MetaRNN	Benign	0.0026	T;T
MetaSVM	Benign	-0.62	T
MutationAssessor	Pathogenic	3.2	M;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.32	T
PROVEAN	Pathogenic	-6.5	D;.
REVEL	Benign	0.21
Sift	Uncertain	0.0020	D;.
Sift4G	Uncertain	0.014	D;D
Polyphen		0.92	P;.
Vest4		0.22
MPC		0.41
ClinPred		0.086	T
GERP RS		3.1
Varity_R		0.76
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs3093153; hg19: chr19-16001215;