19-15649403-C-T

Position:

• chr19-15649403-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.647+122C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,482,150 control chromosomes in the GnomAD database, including 17,344 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 0.16 (2028 hom., cov: 31)
  • Exomes 𝑓: 0.15 (15316 hom.)
• Consequence: CYP4F3 NM_000896.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.113

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP4F3	NM_000896.3	c.647+122C>T		intron_variant		ENST00000221307.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP4F3	ENST00000221307.13	c.647+122C>T		intron_variant		1	NM_000896.3	A1

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24223 AN: 151836 Hom.: 2025 Cov.: 31

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.165

GnomAD4 exome AF: 0.151 AC: 201094 AN: 1330196 Hom.: 15316 AF XY: 0.151 AC XY: 99729 AN XY: 662480

Gnomad4 AFR exome AF: 0.182

Gnomad4 AMR exome AF: 0.104

Gnomad4 ASJ exome AF: 0.161

Gnomad4 EAS exome AF: 0.182

Gnomad4 SAS exome AF: 0.121

Gnomad4 FIN exome AF: 0.123

Gnomad4 NFE exome AF: 0.154

Gnomad4 OTH exome AF: 0.153

GnomAD4 genome AF: 0.159 AC: 24235 AN: 151954 Hom.: 2028 Cov.: 31 AF XY: 0.159 AC XY: 11786 AN XY: 74236

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.165

Alfa AF: 0.154 Hom.: 3896

Bravo AF: 0.162

Asia WGS AF: 0.156 AC: 544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.0
DANN	Benign	0.58

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: rs2283612; hg19: chr19-15760213; COSMIC: COSV55413074; COSMIC: COSV55413074;