rs1558139

Variant names:

• chr19-15886754-G-A
• rs1558139
• NM_001082.5:c.919-446C>T

Variant summary

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

The NM_001082.5(CYP4F2):​c.919-446C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 151,940 control chromosomes in the GnomAD database, including 15,925 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 0.46 (15925 hom., cov: 31)
• Consequence: CYP4F2 NM_001082.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.426
• Publications: 42 publications found

Genes affected

CYP4F2 (HGNC:2645): (cytochrome P450 family 4 subfamily F member 2) This gene 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, CYP4F11, is approximately 16 kb away. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP4F2	NM_001082.5	c.919-446C>T		intron_variant	Intron 7 of 12	ENST00000221700.11	NP_001073.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP4F2	ENST00000221700.11	c.919-446C>T		intron_variant	Intron 7 of 12	1	NM_001082.5	ENSP00000221700.3
CYP4F2	ENST00000011989.11	c.919-446C>T		intron_variant	Intron 7 of 12	1		ENSP00000011989.8
CYP4F2	ENST00000392846.7	n.862-446C>T		intron_variant	Intron 5 of 10	2
CYP4F2	ENST00000587671.2	n.*504-701C>T		intron_variant	Intron 6 of 7	5		ENSP00000467443.2

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69194 AN: 151820 Hom.: 15920 Cov.: 31

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.500

Gnomad OTH AF: 0.439

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

GnomAD4 genome AF: 0.456 AC: 69212 AN: 151940 Hom.: 15925 Cov.: 31 AF XY: 0.451 AC XY: 33521 AN XY: 74274

African (AFR) AF: 0.394 AC: 16319 AN: 41390

American (AMR) AF: 0.419 AC: 6400 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.445 AC: 1541 AN: 3464

East Asian (EAS) AF: 0.393 AC: 2032 AN: 5174

South Asian (SAS) AF: 0.537 AC: 2586 AN: 4816

European-Finnish (FIN) AF: 0.461 AC: 4857 AN: 10538

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.500 AC: 34007 AN: 67966

Other (OTH) AF: 0.439 AC: 927 AN: 2114

Alfa AF: 0.477 Hom.: 29834

Bravo AF: 0.447

Asia WGS AF: 0.446 AC: 1553 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.9
DANN	Benign	0.64
PhyloP100		-0.43
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: rs1558139; hg19: chr19-15997564;