rs1126433

Variant names:

• chr19-15878595-C-T
• rs1126433
• NM_001082.5:c.*176G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001082.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP4F2	NM_001082.5	MANE Select	c.*176G>A		3_prime_UTR	Exon 13 of 13	NP_001073.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP4F2	ENST00000221700.11	TSL:1 MANE Select	c.*176G>A		3_prime_UTR	Exon 13 of 13	ENSP00000221700.3	P78329-1
	CYP4F2	ENST00000011989.11	TSL:1	c.*176G>A		3_prime_UTR	Exon 13 of 13	ENSP00000011989.8	A0A0A0MQR0
	CYP4F2	ENST00000886782.1		c.*176G>A		3_prime_UTR	Exon 14 of 14	ENSP00000556841.1

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

African (AFR) AF: 0.225 AC: 3934 AN: 17464

American (AMR) AF: 0.468 AC: 7788 AN: 16646

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 4386 AN: 14834

East Asian (EAS) AF: 0.714 AC: 21427 AN: 30012

South Asian (SAS) AF: 0.371 AC: 17186 AN: 46272

European-Finnish (FIN) AF: 0.320 AC: 11984 AN: 37480

Middle Eastern (MID) AF: 0.197 AC: 658 AN: 3334

European-Non Finnish (NFE) AF: 0.287 AC: 142690 AN: 497718

Other (OTH) AF: 0.333 AC: 11110 AN: 33366

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

African (AFR) AF: 0.257 AC: 10467 AN: 40806

American (AMR) AF: 0.425 AC: 6423 AN: 15120

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 1080 AN: 3440

East Asian (EAS) AF: 0.744 AC: 3818 AN: 5132

South Asian (SAS) AF: 0.410 AC: 1962 AN: 4784

European-Finnish (FIN) AF: 0.349 AC: 3639 AN: 10414

Middle Eastern (MID) AF: 0.202 AC: 59 AN: 292

European-Non Finnish (NFE) AF: 0.359 AC: 24231 AN: 67534

Other (OTH) AF: 0.330 AC: 685 AN: 2074

Alfa AF: 0.357 Hom.: 1189

Bravo AF: 0.351

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.0
DANN	Benign	0.56
PhyloP100		-0.41
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: rs1126433; hg19: chr19-15989405; COSMIC: COSV55616850; COSMIC: COSV55616850;