dbSNP rs1805042: CYP4F3:p.Val358Val (chr19-15652911-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_000896.3(CYP4F3):c.1074G>A(p.Val358Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 1,611,346 control chromosomes in the GnomAD database, including 125,429 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 0.45 ( 16688 hom., cov: 31)

Exomes 𝑓: 0.38 ( 108741 hom. )

Consequence

CYP4F3
NM_000896.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.607

Publications

30 publications found

Variant links:

Genes affected

CYP4F3 (HGNC:2646): (cytochrome P450 family 4 subfamily F member 3) This gene, CYP4F3, 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, CYP4F8, is approximately 18 kb away. Several transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Apr 2019]

CYP4F3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP7

Synonymous conserved (PhyloP=0.607 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP4F3	NM_000896.3 link	c.1074G>A	p.Val358Val	synonymous_variant	Exon 9 of 13	ENST00000221307.13	NP_000887.2	Q08477-1A0A024R7J8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP4F3	ENST00000221307.13 link	c.1074G>A	p.Val358Val	synonymous_variant	Exon 9 of 13	1	NM_000896.3	ENSP00000221307.6		Q08477-1

Frequencies

GnomAD3 genomes

AF:

0.453

AC:

68774

AN:

151926

Hom.:

16677

Cov.:

show subpopulations

Gnomad AFR

AF:

0.599

Gnomad AMI

AF:

0.410

Gnomad AMR

AF:

0.511

Gnomad ASJ

AF:

0.371

Gnomad EAS

AF:

0.651

Gnomad SAS

AF:

0.373

Gnomad FIN

AF:

0.385

Gnomad MID

AF:

0.459

Gnomad NFE

AF:

0.358

Gnomad OTH

AF:

0.427

GnomAD2 exomes

AF:

0.429

AC:

106912

AN:

249262

AF XY:

0.414

show subpopulations

Gnomad AFR exome

AF:

0.604

Gnomad AMR exome

AF:

0.572

Gnomad ASJ exome

AF:

0.367

Gnomad EAS exome

AF:

0.651

Gnomad FIN exome

AF:

0.383

Gnomad NFE exome

AF:

0.356

Gnomad OTH exome

AF:

0.404

GnomAD4 exome

AF:

0.378

AC:

551676

AN:

1459302

Hom.:

108741

Cov.:

AF XY:

0.376

AC XY:

272976

AN XY:

725872

show subpopulations

African (AFR)

AF:

0.607

AC:

20292

AN:

33412

American (AMR)

AF:

0.564

AC:

25069

AN:

44438

Ashkenazi Jewish (ASJ)

AF:

0.368

AC:

9539

AN:

25920

East Asian (EAS)

AF:

0.649

AC:

25753

AN:

39668

South Asian (SAS)

AF:

0.370

AC:

31769

AN:

85852

European-Finnish (FIN)

AF:

0.383

AC:

20375

AN:

53228

Middle Eastern (MID)

AF:

0.400

AC:

2304

AN:

5754

European-Non Finnish (NFE)

AF:

0.354

AC:

392831

AN:

1110752

Other (OTH)

AF:

0.394

AC:

23744

AN:

60278

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

20998

41996

62993

83991

104989

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.453

AC:

68838

AN:

152044

Hom.:

16688

Cov.:

AF XY:

0.456

AC XY:

33913

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.598

AC:

24804

AN:

41446

American (AMR)

AF:

0.511

AC:

7814

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.371

AC:

1288

AN:

3472

East Asian (EAS)

AF:

0.650

AC:

3355

AN:

5162

South Asian (SAS)

AF:

0.372

AC:

1796

AN:

4822

European-Finnish (FIN)

AF:

0.385

AC:

4064

AN:

10564

Middle Eastern (MID)

AF:

0.459

AC:

135

AN:

294

European-Non Finnish (NFE)

AF:

0.358

AC:

24304

AN:

67982

Other (OTH)

AF:

0.429

AC:

905

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1837

3674

5511

7348

9185

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.406

Hom.:

8435

Bravo

AF:

0.469

Asia WGS

AF:

0.516

AC:

1792

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

9.1

(source)

DANN

Benign

0.84

PhyloP100

0.61

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs1805042

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over