19-15897624-A-G

Position:

• chr19-15897624-A-G

Variant summary

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

The NM_001082.5(CYP4F2):​c.-1-12T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 1,611,402 control chromosomes in the GnomAD database, including 21,117 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 0.15 (1832 hom., cov: 31)
  • Exomes 𝑓: 0.16 (19285 hom.)
• Consequence: CYP4F2 NM_001082.5 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00007540
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0600

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=-0.9).
• 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.-1-12T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000221700.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP4F2	ENST00000221700.11	c.-1-12T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001082.5	P3

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22877 AN: 151884 Hom.: 1831 Cov.: 31

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.0820

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.184

GnomAD3 exomes AF: 0.145 AC: 36149 AN: 248510 Hom.: 2976 AF XY: 0.150 AC XY: 20171 AN XY: 134508

Gnomad AFR exome AF: 0.134

Gnomad AMR exome AF: 0.0995

Gnomad ASJ exome AF: 0.199

Gnomad EAS exome AF: 0.0860

Gnomad SAS exome AF: 0.159

Gnomad FIN exome AF: 0.113

Gnomad NFE exome AF: 0.167

Gnomad OTH exome AF: 0.162

GnomAD4 exome AF: 0.159 AC: 232369 AN: 1459400 Hom.: 19285 Cov.: 33 AF XY: 0.160 AC XY: 116134 AN XY: 726034

Gnomad4 AFR exome AF: 0.137

Gnomad4 AMR exome AF: 0.105

Gnomad4 ASJ exome AF: 0.199

Gnomad4 EAS exome AF: 0.106

Gnomad4 SAS exome AF: 0.157

Gnomad4 FIN exome AF: 0.112

Gnomad4 NFE exome AF: 0.165

Gnomad4 OTH exome AF: 0.157

GnomAD4 genome AF: 0.151 AC: 22895 AN: 152002 Hom.: 1832 Cov.: 31 AF XY: 0.149 AC XY: 11099 AN XY: 74292

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.0829

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.166

Gnomad4 OTH AF: 0.186

Alfa AF: 0.166 Hom.: 382

Bravo AF: 0.152

Asia WGS AF: 0.137 AC: 475 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	3.4
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000075
dbscSNV1_RF	Benign	0.012
SpliceAI score (max)		0.030		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: rs3093103; hg19: chr19-16008434; COSMIC: COSV50002751; COSMIC: COSV50002751;