chr19-15914366-C-G

Variant names:

• chr19-15914366-C-G
• rs1060463
• NM_021187.4:c.1336G>C

Variant summary

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

The NM_021187.4(CYP4F11):​c.1336G>C​(p.Asp446His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency: Genomes: not found (cov: 30)
• Consequence: CYP4F11 NM_021187.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.456
• Publications: 57 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.1336G>C	p.Asp446His	missense	Exon 11 of 12	NP_067010.3	Q9HBI6
	CYP4F11	NM_001128932.2		c.1336G>C	p.Asp446His	missense	Exon 12 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.1336G>C	p.Asp446His	missense	Exon 11 of 12	ENSP00000384588.2	Q9HBI6
	CYP4F11	ENST00000248041.12	TSL:1	c.1336G>C	p.Asp446His	missense	Exon 12 of 13	ENSP00000248041.6	Q9HBI6
	CYP4F11	ENST00000326742.12	TSL:1	c.1271G>C	p.Arg424Pro	missense	Exon 10 of 11	ENSP00000319859.7	F8W978

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 57

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 106033

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	14
DANN	Benign	0.52
DEOGEN2	Benign	0.26	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.67	T
MutationAssessor	Pathogenic	3.5	M
PhyloP100		0.46
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Benign	0.28
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.038	D
Polyphen		0.99	D
Vest4		0.24
MutPred		0.48		Gain of methylation at K451 (P = 0.1272)
MVP		0.43
MPC		0.17
ClinPred		0.94	D
GERP RS		0.70
Varity_R		0.28
gMVP		0.68
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1060463; hg19: chr19-16025176;