rs1805042

Variant names:

• chr19-15652911-G-A
• rs1805042
• NM_000896.3:c.1074G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.607
• Publications: 30 publications found

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]

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000896.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP4F3	NM_000896.3	MANE Select	c.1074G>A	p.Val358Val	synonymous	Exon 9 of 13	NP_000887.2	Q08477-1
	CYP4F3	NM_001199208.2		c.1074G>A	p.Val358Val	synonymous	Exon 9 of 13	NP_001186137.1	Q08477-2
	CYP4F3	NM_001199209.2		c.1074G>A	p.Val358Val	synonymous	Exon 9 of 13	NP_001186138.1	Q08477-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP4F3	ENST00000221307.13	TSL:1 MANE Select	c.1074G>A	p.Val358Val	synonymous	Exon 9 of 13	ENSP00000221307.6	Q08477-1
	CYP4F3	ENST00000585846.1	TSL:1	c.1074G>A	p.Val358Val	synonymous	Exon 8 of 12	ENSP00000468105.1	Q08477-2
	CYP4F3	ENST00000591058.5	TSL:1	c.1074G>A	p.Val358Val	synonymous	Exon 9 of 13	ENSP00000466988.1	Q08477-2

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68774 AN: 151926 Hom.: 16677 Cov.: 31

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

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.: 80 AF XY: 0.376 AC XY: 272976 AN XY: 725872

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

GnomAD4 genome AF: 0.453 AC: 68838 AN: 152044 Hom.: 16688 Cov.: 31 AF XY: 0.456 AC XY: 33913 AN XY: 74326

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	9.1
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)

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

Other links and lift over

dbSNP: rs1805042; hg19: chr19-15763721; COSMIC: COSV55407969; COSMIC: COSV55407969;