chr19-15649403-C-T

Variant names:

• chr19-15649403-C-T
• rs2283612
• NM_000896.3:c.647+122C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CYP4F3	NM_000896.3	c.647+122C>T		intron_variant	Intron 6 of 12	ENST00000221307.13	NP_000887.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP4F3	ENST00000221307.13	c.647+122C>T		intron_variant	Intron 6 of 12	1	NM_000896.3	ENSP00000221307.6

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

African (AFR) AF: 0.182 AC: 5446 AN: 29972

American (AMR) AF: 0.104 AC: 3735 AN: 35760

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 3634 AN: 22560

East Asian (EAS) AF: 0.182 AC: 6978 AN: 38286

South Asian (SAS) AF: 0.121 AC: 9421 AN: 78068

European-Finnish (FIN) AF: 0.123 AC: 5510 AN: 44650

Middle Eastern (MID) AF: 0.176 AC: 940 AN: 5326

European-Non Finnish (NFE) AF: 0.154 AC: 156979 AN: 1020374

Other (OTH) AF: 0.153 AC: 8451 AN: 55200

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

African (AFR) AF: 0.181 AC: 7505 AN: 41430

American (AMR) AF: 0.148 AC: 2262 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 578 AN: 3466

East Asian (EAS) AF: 0.179 AC: 918 AN: 5140

South Asian (SAS) AF: 0.119 AC: 571 AN: 4814

European-Finnish (FIN) AF: 0.127 AC: 1337 AN: 10548

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10536 AN: 67966

Other (OTH) AF: 0.165 AC: 348 AN: 2110

Alfa AF: 0.154 Hom.: 7924

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
PhyloP100		0.11
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: rs2283612; hg19: chr19-15760213; COSMIC: COSV55413074; COSMIC: COSV55413074;