Genetic Variant CYP4F2:c.-1-76T>C (chr19-15897688-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001082.5(CYP4F2):c.-1-76T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00636 in 1,558,200 control chromosomes in the GnomAD database, including 453 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.029 ( 234 hom., cov: 32)

Exomes 𝑓: 0.0039 ( 219 hom. )

Consequence

CYP4F2
NM_001082.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0240

Publications

5 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0949 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001082.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP4F2	NM_001082.5	MANE Select	c.-1-76T>C		intron	N/A	NP_001073.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CYP4F2	ENST00000221700.11	TSL:1 MANE Select	c.-1-76T>C	intron	N/A	ENSP00000221700.3
CYP4F2	ENST00000011989.11	TSL:1	c.-1-76T>C	intron	N/A	ENSP00000011989.8
CYP4F2	ENST00000586927.2	TSL:4	c.-77T>C	5_prime_UTR	Exon 1 of 4	ENSP00000465514.1

Frequencies

GnomAD3 genomes

AF:

0.0288

AC:

4374

AN:

152064

Hom.:

229

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0970

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0100

Gnomad ASJ

AF:

0.0130

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.00704

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00109

Gnomad OTH

AF:

0.0192

GnomAD4 exome

AF:

0.00392

AC:

5506

AN:

1406018

Hom.:

219

Cov.:

AF XY:

0.00380

AC XY:

2663

AN XY:

700630

show subpopulations

African (AFR)

AF:

0.101

AC:

3193

AN:

31642

American (AMR)

AF:

0.00777

AC:

307

AN:

39504

Ashkenazi Jewish (ASJ)

AF:

0.0108

AC:

271

AN:

25100

East Asian (EAS)

AF:

0.000901

AC:

AN:

38850

South Asian (SAS)

AF:

0.00621

AC:

517

AN:

83240

European-Finnish (FIN)

AF:

0.0000222

AC:

AN:

45004

Middle Eastern (MID)

AF:

0.0110

AC:

AN:

4278

European-Non Finnish (NFE)

AF:

0.000522

AC:

564

AN:

1079894

Other (OTH)

AF:

0.00976

AC:

571

AN:

58506

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

201

401

602

802

1003

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

252

378

504

630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0289

AC:

4399

AN:

152182

Hom.:

234

Cov.:

AF XY:

0.0282

AC XY:

2100

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.0974

AC:

4043

AN:

41496

American (AMR)

AF:

0.0100

AC:

153

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0130

AC:

AN:

3470

East Asian (EAS)

AF:

0.00135

AC:

AN:

5168

South Asian (SAS)

AF:

0.00663

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00109

AC:

AN:

67994

Other (OTH)

AF:

0.0190

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

188

376

564

752

940

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0279

Hom.:

Bravo

AF:

0.0327

Asia WGS

AF:

0.0140

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

3.4

(source)

DANN

Benign

0.38

PhyloP100

-0.024

PromoterAI

0.0030

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over