rs745742980

Variant names:

• chr19-15615621-C-G
• rs745742980
• NM_007253.4:c.5C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-15615621-C-G
• chr19-15615621-C-T

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.5C>G​(p.Ser2Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 10/15 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. S2L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CYP4F8 NM_007253.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.36
• Publications: 0 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=0.15705878).

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.5C>G	p.Ser2Trp	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.5C>G	p.Ser2Trp	missense	Exon 2 of 13	ENSP00000477567.1	P98187
	CYP4F8	ENST00000617645.4	TSL:3	c.20C>G	p.Ser7Trp	missense	Exon 2 of 6	ENSP00000478555.1	A0A087WUC9
	CYP4F8	ENST00000325723.10	TSL:2	n.5C>G		non_coding_transcript_exon	Exon 2 of 9	ENSP00000479430.1	A0A087WVG9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249488 AF XY: 0.00000740

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	4.0
DANN	Uncertain	0.98
DEOGEN2	Benign	0.061	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.51	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.69	T
PhyloP100		-4.4
PrimateAI	Benign	0.44	T
Sift4G	Uncertain	0.019	D
Polyphen		0.99	D
Vest4		0.22
MutPred		0.39		Loss of disorder (P = 0)
MVP		0.14
ClinPred		0.24	T
GERP RS		-4.3
PromoterAI		0.027	Neutral
Varity_R		0.043
gMVP		0.35
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: rs745742980; hg19: chr19-15726432;