rs2683037

Variant names:

• chr19-15652128-T-A
• rs2683037
• NM_000896.3:c.919-441T>A

Your query was ambiguous. Multiple possible variants found:

• chr19-15652128-T-A
• chr19-15652128-T-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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=-0.87).
• 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 rank	MANE	Protein	UniProt
CYP4F3	NM_000896.3	c.919-441T>A		intron_variant	Intron 7 of 12	ENST00000221307.13	NP_000887.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP4F3	ENST00000221307.13	c.919-441T>A		intron_variant	Intron 7 of 12	1	NM_000896.3	ENSP00000221307.6

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

African (AFR) AF: 0.154 AC: 6384 AN: 41476

American (AMR) AF: 0.187 AC: 2853 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 724 AN: 3466

East Asian (EAS) AF: 0.165 AC: 851 AN: 5170

South Asian (SAS) AF: 0.266 AC: 1281 AN: 4824

European-Finnish (FIN) AF: 0.200 AC: 2115 AN: 10568

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.248 AC: 16863 AN: 67952

Other (OTH) AF: 0.249 AC: 526 AN: 2114

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
PhyloP100		-0.0030
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: rs2683037; hg19: chr19-15762938;