19-15922135-C-T

Variant names:

• chr19-15922135-C-T
• rs538980112
• NM_021187.4:c.1017G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_021187.4(CYP4F11):​c.1017G>A​(p.Trp339*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CYP4F11 NM_021187.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.91
• Publications: 2 publications found

Genes affected

CYP4F11 (HGNC:13265): (cytochrome P450 family 4 subfamily F member 11) This gene, CYP4F11, 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 gene is part of a cluster of cytochrome P450 genes on chromosome 19. Another member of this family, CYP4F2, is approximately 16 kb away. Alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021187.4. 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
	CYP4F11	NM_021187.4	MANE Select	c.1017G>A	p.Trp339*	stop_gained	Exon 8 of 12	NP_067010.3	Q9HBI6
	CYP4F11	NM_001128932.2		c.1017G>A	p.Trp339*	stop_gained	Exon 9 of 13	NP_001122404.1	Q9HBI6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP4F11	ENST00000402119.9	TSL:1 MANE Select	c.1017G>A	p.Trp339*	stop_gained	Exon 8 of 12	ENSP00000384588.2	Q9HBI6
	CYP4F11	ENST00000248041.12	TSL:1	c.1017G>A	p.Trp339*	stop_gained	Exon 9 of 13	ENSP00000248041.6	Q9HBI6
	CYP4F11	ENST00000326742.12	TSL:1	c.1017G>A	p.Trp339*	stop_gained	Exon 8 of 11	ENSP00000319859.7	F8W978

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.52	D
BayesDel_noAF	Pathogenic	0.50
CADD	Pathogenic	38
DANN	Uncertain	1.0
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.95	D
PhyloP100		6.9
Vest4		0.47
GERP RS		2.8
Mutation Taster		=8/192	disease causing (fs/PTC)

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: rs538980112; hg19: chr19-16032945;