NM_007253.4:c.164G>A

Variant names:

• chr19-15615780-G-A
• rs377226039
• NM_007253.4:c.164G>A

Variant summary

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

The NM_007253.4(CYP4F8):​c.164G>A​(p.Arg55Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,404 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/15 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: 0.0000055 (0 hom.)
• Consequence: CYP4F8 NM_007253.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.511
• Publications: 1 publications found

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

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=0.07185048).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007253.4. 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
	CYP4F8	NM_007253.4	MANE Select	c.164G>A	p.Arg55Gln	missense	Exon 2 of 13	NP_009184.1	P98187

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP4F8	ENST00000612078.5	TSL:1 MANE Select	c.164G>A	p.Arg55Gln	missense	Exon 2 of 13	ENSP00000477567.1	P98187
	CYP4F8	ENST00000617645.4	TSL:3	c.179G>A	p.Arg60Gln	missense	Exon 2 of 6	ENSP00000478555.1	A0A087WUC9
	CYP4F8	ENST00000325723.10	TSL:2	n.164G>A		non_coding_transcript_exon	Exon 2 of 9	ENSP00000479430.1	A0A087WVG9

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000281 AC: 7 AN: 249276 AF XY: 0.0000222

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000272

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461404 Hom.: 0 Cov.: 34 AF XY: 0.00000550 AC XY: 4 AN XY: 726992

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39672

South Asian (SAS) AF: 0.00 AC: 0 AN: 86224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111722

Other (OTH) AF: 0.0000331 AC: 2 AN: 60382

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.054	T
Eigen	Benign	-0.87
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.074	N
LIST_S2	Benign	0.46	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-0.89	T
PhyloP100		0.51
PrimateAI	Benign	0.29	T
Sift4G	Uncertain	0.039	D
Polyphen		0.0040	B
Vest4		0.088
MVP		0.16
ClinPred		0.072	T
GERP RS		1.3
Varity_R		0.044
gMVP		0.26
Mutation Taster		=100/0	polymorphism

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: rs377226039; hg19: chr19-15726591; COSMIC: COSV57853989; COSMIC: COSV57853989;