19-15878595-C-T

Position:

• chr19-15878595-C-T

Variant summary

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

The NM_001082.5(CYP4F2):​c.*176G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 847,626 control chromosomes in the GnomAD database, including 45,946 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 0.35 (9925 hom., cov: 31)
  • Exomes 𝑓: 0.32 (36021 hom.)
• Consequence: CYP4F2 NM_001082.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.415

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP4F2	NM_001082.5	c.*176G>A		3_prime_UTR_variant	13/13	ENST00000221700.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP4F2	ENST00000221700.11	c.*176G>A		3_prime_UTR_variant	13/13	1	NM_001082.5	P3
CYP4F2	ENST00000011989.11	c.*176G>A		3_prime_UTR_variant	13/13	1		A1
CYP4F2	ENST00000392846.7	n.1682G>A		non_coding_transcript_exon_variant	11/11	2
CYP4F2	ENST00000589654.2			downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.350 AC: 52616 AN: 150386 Hom.: 9925 Cov.: 31

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.745

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.208

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.328

GnomAD4 exome AF: 0.317 AC: 221163 AN: 697126 Hom.: 36021 Cov.: 11 AF XY: 0.322 AC XY: 112428 AN XY: 349234

Gnomad4 AFR exome AF: 0.225

Gnomad4 AMR exome AF: 0.468

Gnomad4 ASJ exome AF: 0.296

Gnomad4 EAS exome AF: 0.714

Gnomad4 SAS exome AF: 0.371

Gnomad4 FIN exome AF: 0.320

Gnomad4 NFE exome AF: 0.287

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.350 AC: 52633 AN: 150500 Hom.: 9925 Cov.: 31 AF XY: 0.351 AC XY: 25797 AN XY: 73402

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.425

Gnomad4 ASJ AF: 0.314

Gnomad4 EAS AF: 0.744

Gnomad4 SAS AF: 0.410

Gnomad4 FIN AF: 0.349

Gnomad4 NFE AF: 0.359

Gnomad4 OTH AF: 0.330

Alfa AF: 0.357 Hom.: 1189

Bravo AF: 0.351

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.0
DANN	Benign	0.56

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: rs1126433; hg19: chr19-15989405; COSMIC: COSV55616850; COSMIC: COSV55616850;