19-15641087-T-G

Position:

• chr19-15641087-T-G

Variant summary

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

The NM_000896.3(CYP4F3):​c.-2+142T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 298,938 control chromosomes in the GnomAD database, including 21,324 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 0.36 (10124 hom., cov: 32)
  • Exomes 𝑓: 0.38 (11200 hom.)
• Consequence: CYP4F3 NM_000896.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.762

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP4F3	NM_000896.3	c.-2+142T>G		intron_variant		ENST00000221307.13	NP_000887.2
CYP4F3	NM_001199208.2	c.-2+142T>G		intron_variant			NP_001186137.1
CYP4F3	NM_001199209.2	c.-2+158T>G		intron_variant			NP_001186138.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP4F3	ENST00000221307.13	c.-2+142T>G		intron_variant		1	NM_000896.3	ENSP00000221307.6
CYP4F3	ENST00000591058.5	c.-2+142T>G		intron_variant		1		ENSP00000466988.1
CYP4F3	ENST00000586182.6	c.-2+158T>G		intron_variant		2		ENSP00000466395.1
CYP4F3	ENST00000592279.6	n.49+142T>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54227 AN: 151954 Hom.: 10129 Cov.: 32

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.397

GnomAD4 exome AF: 0.380 AC: 55744 AN: 146866 Hom.: 11200 AF XY: 0.382 AC XY: 29633 AN XY: 77584

Gnomad4 AFR exome AF: 0.283

Gnomad4 AMR exome AF: 0.280

Gnomad4 ASJ exome AF: 0.366

Gnomad4 EAS exome AF: 0.328

Gnomad4 SAS exome AF: 0.384

Gnomad4 FIN exome AF: 0.325

Gnomad4 NFE exome AF: 0.399

Gnomad4 OTH exome AF: 0.378

GnomAD4 genome AF: 0.357 AC: 54233 AN: 152072 Hom.: 10124 Cov.: 32 AF XY: 0.354 AC XY: 26325 AN XY: 74346

Gnomad4 AFR AF: 0.283

Gnomad4 AMR AF: 0.332

Gnomad4 ASJ AF: 0.378

Gnomad4 EAS AF: 0.342

Gnomad4 SAS AF: 0.399

Gnomad4 FIN AF: 0.329

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.398

Alfa AF: 0.405 Hom.: 16212

Bravo AF: 0.354

Asia WGS AF: 0.393 AC: 1366 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.91
DANN	Benign	0.32

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: rs1290617; hg19: chr19-15751897;