rs1290625

Variant names:

• chr19-15646346-G-A
• rs1290625
• NM_000896.3:c.343+483G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-15646346-G-A
• chr19-15646346-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000896.3(CYP4F3):​c.343+483G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0687 in 152,212 control chromosomes in the GnomAD database, including 423 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 0.069 (423 hom., cov: 32)
• Consequence: CYP4F3 NM_000896.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.881
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP4F3	NM_000896.3	c.343+483G>A		intron_variant	Intron 3 of 12	ENST00000221307.13	NP_000887.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP4F3	ENST00000221307.13	c.343+483G>A		intron_variant	Intron 3 of 12	1	NM_000896.3	ENSP00000221307.6

Frequencies

GnomAD3 genomes AF: 0.0688 AC: 10459 AN: 152094 Hom.: 424 Cov.: 32

Gnomad AFR AF: 0.0765

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.0306

Gnomad ASJ AF: 0.0397

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.0611

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0631

Gnomad OTH AF: 0.0531

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

GnomAD4 genome AF: 0.0687 AC: 10463 AN: 152212 Hom.: 423 Cov.: 32 AF XY: 0.0698 AC XY: 5194 AN XY: 74422

African (AFR) AF: 0.0764 AC: 3169 AN: 41502

American (AMR) AF: 0.0305 AC: 467 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0397 AC: 138 AN: 3472

East Asian (EAS) AF: 0.116 AC: 599 AN: 5184

South Asian (SAS) AF: 0.194 AC: 934 AN: 4812

European-Finnish (FIN) AF: 0.0611 AC: 648 AN: 10608

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0631 AC: 4294 AN: 68016

Other (OTH) AF: 0.0572 AC: 121 AN: 2114

Alfa AF: 0.0663 Hom.: 44

Bravo AF: 0.0648

Asia WGS AF: 0.153 AC: 529 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.6
DANN	Benign	0.66
PhyloP100		-0.88
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)		0.0		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: rs1290625; hg19: chr19-15757156;