19-15615806-C-G

Variant names:

• chr19-15615806-C-G
• NM_007253.4:c.190C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007253.4(CYP4F8):​c.190C>G​(p.Leu64Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,270 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CYP4F8 NM_007253.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.953

Genes affected

CYP4F8 (HGNC:2648): (cytochrome P450 family 4 subfamily F member 8) This gene, CYP4F8, 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 and functions as a 19-hydroxylase of prostaglandins in seminal vesicles. This gene is part of a cluster of cytochrome P450 genes on chromosome 19. Another member of this family, CYP4F3, is approximately 18 kb away. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20662504).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP4F8	NM_007253.4	c.190C>G	p.Leu64Val	missense_variant	Exon 2 of 13	ENST00000612078.5	NP_009184.1
CYP4F8	XM_024451341.2	c.190C>G	p.Leu64Val	missense_variant	Exon 2 of 11		XP_024307109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP4F8	ENST00000612078.5	c.190C>G	p.Leu64Val	missense_variant	Exon 2 of 13	1	NM_007253.4	ENSP00000477567.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459270 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 725852

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.190C>G (p.L64V) alteration is located in exon 2 (coding exon 1) of the CYP4F8 gene. This alteration results from a C to G substitution at nucleotide position 190, causing the leucine (L) at amino acid position 64 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	12
DANN	Benign	0.89
DEOGEN2	Benign	0.072	.;T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.48	T;T
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-0.93	T
PrimateAI	Benign	0.26	T
Sift4G	Benign	0.24	T;T
Polyphen		0.011	.;B
Vest4		0.051
MutPred		0.62		.;Gain of helix (P = 0.1736);
MVP		0.15
ClinPred		0.31	T
GERP RS		-3.8
Varity_R		0.031
gMVP		0.48

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-15726617;