chr19-15913892-G-T

Variant names:

• chr19-15913892-G-T
• rs758162397
• NM_021187.4:c.1415C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021187.4(CYP4F11):​c.1415C>A​(p.Ala472Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A472V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CYP4F11 NM_021187.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.39
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1566605).

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.1415C>A	p.Ala472Glu	missense	Exon 12 of 12	NP_067010.3	Q9HBI6
	CYP4F11	NM_001128932.2		c.1415C>A	p.Ala472Glu	missense	Exon 13 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.1415C>A	p.Ala472Glu	missense	Exon 12 of 12	ENSP00000384588.2	Q9HBI6
	CYP4F11	ENST00000248041.12	TSL:1	c.1415C>A	p.Ala472Glu	missense	Exon 13 of 13	ENSP00000248041.6	Q9HBI6
	CYP4F11	ENST00000326742.12	TSL:1	c.1350C>A	p.Gly450Gly	synonymous	Exon 11 of 11	ENSP00000319859.7	F8W978

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461070 Hom.: 0 Cov.: 61 AF XY: 0.00 AC XY: 0 AN XY: 726764

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26054

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86128

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53338

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5684

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111670

Other (OTH) AF: 0.00 AC: 0 AN: 60352

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	-0.093	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	14
DANN	Benign	0.57
DEOGEN2	Benign	0.022	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.092	N
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.9	L
PhyloP100		1.4
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.18
Sift	Benign	0.061	T
Sift4G	Benign	0.14	T
Polyphen		0.17	B
Vest4		0.12
MutPred		0.66		Loss of catalytic residue at A472 (P = 0.1182)
MVP		0.22
MPC		0.041
ClinPred		0.14	T
GERP RS		-1.3
Varity_R		0.12
gMVP		0.60
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs758162397; hg19: chr19-16024702;