rs1805042

chr19-15652911-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000896.3(CYP4F3):c.1074G>A(p.Val358=) 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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
CYP4F3	NM_000896.3	c.1074G>A	p.Val358=	synonymous_variant	9/13	ENST00000221307.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP4F3	ENST00000221307.13	c.1074G>A	p.Val358=	synonymous_variant	9/13	1	NM_000896.3	A1

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

GnomAD3 exomes AF: 0.429 AC: 106912 AN: 249262 Hom.: 24878 AF XY: 0.414 AC XY: 55725 AN XY: 134672

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 SAS exome AF: 0.368

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

Gnomad4 AFR exome AF: 0.607

Gnomad4 AMR exome AF: 0.564

Gnomad4 ASJ exome AF: 0.368

Gnomad4 EAS exome AF: 0.649

Gnomad4 SAS exome AF: 0.370

Gnomad4 FIN exome AF: 0.383

Gnomad4 NFE exome AF: 0.354

Gnomad4 OTH exome AF: 0.394

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

Gnomad4 AFR AF: 0.598

Gnomad4 AMR AF: 0.511

Gnomad4 ASJ AF: 0.371

Gnomad4 EAS AF: 0.650

Gnomad4 SAS AF: 0.372

Gnomad4 FIN AF: 0.385

Gnomad4 NFE AF: 0.358

Gnomad4 OTH AF: 0.429

Alfa AF: 0.395 Hom.: 5853

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
Dann	Benign	0.84
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

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