rs2683037

chr19-15652128-T-Achr19-15652128-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000896.3(CYP4F3):c.919-441T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,060 control chromosomes in the GnomAD database, including 3,641 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 0.21 (3641 hom., cov: 32)
• Consequence: CYP4F3 NM_000896.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00300

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP4F3	NM_000896.3	c.919-441T>A		intron_variant		ENST00000221307.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP4F3	ENST00000221307.13	c.919-441T>A		intron_variant		1	NM_000896.3	A1

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31798 AN: 151940 Hom.: 3641 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.247

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.209 AC: 31821 AN: 152060 Hom.: 3641 Cov.: 32 AF XY: 0.208 AC XY: 15444 AN XY: 74346

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.266

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.249

Alfa AF: 0.239 Hom.: 673

Bravo AF: 0.207

Asia WGS AF: 0.234 AC: 814 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	11
Dann	Benign	0.85

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

LitVar

Other links and lift over

dbSNP: rs2683037; hg19: chr19-15762938;