rs3093103

Variant names:

• chr19-15897624-A-G
• rs3093103
• NM_001082.5:c.-1-12T>C

Variant summary

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

The NM_001082.5(CYP4F2):​c.-1-12T>C variant causes a 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 intron
• Scores: Splicing: ADA: 0.00007540
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0600
• Publications: 13 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 (NFE) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP4F2	NM_001082.5	c.-1-12T>C		intron_variant	Intron 1 of 12	ENST00000221700.11	NP_001073.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP4F2	ENST00000221700.11	c.-1-12T>C		intron_variant	Intron 1 of 12	1	NM_001082.5	ENSP00000221700.3

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

GnomAD2 exomes AF: 0.145 AC: 36149 AN: 248510 AF XY: 0.150

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 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

African (AFR) AF: 0.137 AC: 4587 AN: 33390

American (AMR) AF: 0.105 AC: 4681 AN: 44488

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 5186 AN: 26048

East Asian (EAS) AF: 0.106 AC: 4208 AN: 39650

South Asian (SAS) AF: 0.157 AC: 13543 AN: 86120

European-Finnish (FIN) AF: 0.112 AC: 5903 AN: 52698

Middle Eastern (MID) AF: 0.184 AC: 1023 AN: 5550

European-Non Finnish (NFE) AF: 0.165 AC: 183762 AN: 1111192

Other (OTH) AF: 0.157 AC: 9476 AN: 60264

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

African (AFR) AF: 0.136 AC: 5651 AN: 41454

American (AMR) AF: 0.154 AC: 2357 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 691 AN: 3468

East Asian (EAS) AF: 0.0829 AC: 426 AN: 5136

South Asian (SAS) AF: 0.158 AC: 758 AN: 4812

European-Finnish (FIN) AF: 0.112 AC: 1185 AN: 10594

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.166 AC: 11306 AN: 67944

Other (OTH) AF: 0.186 AC: 391 AN: 2106

Alfa AF: 0.165 Hom.: 397

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
PhyloP100		0.060
PromoterAI		0.016	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3093103; hg19: chr19-16008434; COSMIC: COSV50002751; COSMIC: COSV50002751;