19-15658720-C-T

Position:

• chr19-15658720-C-T

Variant summary

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

The NM_000896.3(CYP4F3):​c.1315-7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 1,613,178 control chromosomes in the GnomAD database, including 128,597 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.46 (17351 hom., cov: 30)
  • Exomes 𝑓: 0.38 (111246 hom.)
• Consequence: CYP4F3 NM_000896.3 splice_region, intron
• Scores: Splicing: ADA: 0.0001283
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.72

Genes affected

CYP4F3 (HGNC:2646): (cytochrome P450 family 4 subfamily F member 3) This gene, CYP4F3, 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, CYP4F8, is approximately 18 kb away. Several transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Apr 2019]

CYP4F3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP4F3	NM_000896.3	c.1315-7C>T		splice_region_variant, intron_variant		ENST00000221307.13	NP_000887.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP4F3	ENST00000221307.13	c.1315-7C>T		splice_region_variant, intron_variant		1	NM_000896.3	ENSP00000221307.6

Frequencies

GnomAD3 genomes AF: 0.461 AC: 69944 AN: 151600 Hom.: 17338 Cov.: 30

Gnomad AFR AF: 0.622

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.654

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.429

GnomAD3 exomes AF: 0.435 AC: 109270 AN: 250970 Hom.: 25548 AF XY: 0.420 AC XY: 57020 AN XY: 135672

Gnomad AFR exome AF: 0.628

Gnomad AMR exome AF: 0.573

Gnomad ASJ exome AF: 0.369

Gnomad EAS exome AF: 0.658

Gnomad SAS exome AF: 0.377

Gnomad FIN exome AF: 0.402

Gnomad NFE exome AF: 0.360

Gnomad OTH exome AF: 0.406

GnomAD4 exome AF: 0.382 AC: 558688 AN: 1461460 Hom.: 111246 Cov.: 47 AF XY: 0.380 AC XY: 276468 AN XY: 727034

Gnomad4 AFR exome AF: 0.630

Gnomad4 AMR exome AF: 0.565

Gnomad4 ASJ exome AF: 0.368

Gnomad4 EAS exome AF: 0.655

Gnomad4 SAS exome AF: 0.376

Gnomad4 FIN exome AF: 0.401

Gnomad4 NFE exome AF: 0.357

Gnomad4 OTH exome AF: 0.399

GnomAD4 genome AF: 0.461 AC: 70010 AN: 151718 Hom.: 17351 Cov.: 30 AF XY: 0.465 AC XY: 34441 AN XY: 74116

Gnomad4 AFR AF: 0.622

Gnomad4 AMR AF: 0.513

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.654

Gnomad4 SAS AF: 0.373

Gnomad4 FIN AF: 0.399

Gnomad4 NFE AF: 0.360

Gnomad4 OTH AF: 0.431

Alfa AF: 0.393 Hom.: 5285

Bravo AF: 0.478

Asia WGS AF: 0.525 AC: 1823 AN: 3478

EpiCase AF: 0.364

EpiControl AF: 0.366

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.34

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00013
dbscSNV1_RF	Benign	0.0060
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: rs4646519; hg19: chr19-15769530; COSMIC: COSV105019623; COSMIC: COSV105019623;