rs2074901

Positions:

• chr19-15886612-A-C

Variant summary

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

The NM_001082.5(CYP4F2):​c.919-304T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 381,880 control chromosomes in the GnomAD database, including 4,349 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 0.14 (1639 hom., cov: 30)
  • Exomes 𝑓: 0.14 (2710 hom.)
• Consequence: CYP4F2 NM_001082.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.431

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP4F2	NM_001082.5	c.919-304T>G		intron_variant		ENST00000221700.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP4F2	ENST00000221700.11	c.919-304T>G		intron_variant		1	NM_001082.5	P3
CYP4F2	ENST00000011989.11	c.919-304T>G		intron_variant		1		A1
CYP4F2	ENST00000587671.2	c.*504-559T>G		intron_variant, NMD_transcript_variant		5
CYP4F2	ENST00000392846.7	n.862-304T>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21348 AN: 152038 Hom.: 1641 Cov.: 30

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.0923

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.0847

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.178

GnomAD4 exome AF: 0.141 AC: 32363 AN: 229724 Hom.: 2710 AF XY: 0.142 AC XY: 16735 AN XY: 117890

Gnomad4 AFR exome AF: 0.0901

Gnomad4 AMR exome AF: 0.118

Gnomad4 ASJ exome AF: 0.185

Gnomad4 EAS exome AF: 0.0998

Gnomad4 SAS exome AF: 0.144

Gnomad4 FIN exome AF: 0.0984

Gnomad4 NFE exome AF: 0.151

Gnomad4 OTH exome AF: 0.139

GnomAD4 genome AF: 0.140 AC: 21360 AN: 152156 Hom.: 1639 Cov.: 30 AF XY: 0.139 AC XY: 10366 AN XY: 74380

Gnomad4 AFR AF: 0.100

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.0855

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.166

Gnomad4 OTH AF: 0.179

Alfa AF: 0.168 Hom.: 3043

Bravo AF: 0.140

Asia WGS AF: 0.140 AC: 486 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	10
DANN	Benign	0.73

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: rs2074901; hg19: chr19-15997422;