rs2283612

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr19-15649403-C-A
• chr19-15649403-C-G
• chr19-15649403-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000896.3(CYP4F3):​c.647+122C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CYP4F3 NM_000896.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.113
• Publications: 9 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000896.3. 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
	CYP4F3	NM_000896.3	MANE Select	c.647+122C>A		intron	N/A	NP_000887.2	Q08477-1
	CYP4F3	NM_001199208.2		c.647+122C>A		intron	N/A	NP_001186137.1	Q08477-2
	CYP4F3	NM_001199209.2		c.647+122C>A		intron	N/A	NP_001186138.1	Q08477-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP4F3	ENST00000221307.13	TSL:1 MANE Select	c.647+122C>A		intron	N/A	ENSP00000221307.6	Q08477-1
	CYP4F3	ENST00000585846.1	TSL:1	c.647+122C>A		intron	N/A	ENSP00000468105.1	Q08477-2
	CYP4F3	ENST00000591058.5	TSL:1	c.647+122C>A		intron	N/A	ENSP00000466988.1	Q08477-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1331496 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 663060

African (AFR) AF: 0.00 AC: 0 AN: 30004

American (AMR) AF: 0.00 AC: 0 AN: 35782

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22580

East Asian (EAS) AF: 0.00 AC: 0 AN: 38318

South Asian (SAS) AF: 0.00 AC: 0 AN: 78094

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44686

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5330

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1021454

Other (OTH) AF: 0.00 AC: 0 AN: 55248

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.0
DANN	Benign	0.66
PhyloP100		0.11

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2283612;

hg19: chr19-15760213;