rs200373927

Variant names:

• chr19-15885946-G-A
• rs200373927
• NM_001082.5:c.1093C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-15885946-G-A
• chr19-15885946-G-C
• chr19-15885946-G-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001082.5(CYP4F2):​c.1093C>T​(p.Arg365Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000372 in 1,613,924 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000029 (0 hom.)
• Consequence: CYP4F2 NM_001082.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.00
• Publications: 2 publications found

Genes affected

CYP4F2 (HGNC:2645): (cytochrome P450 family 4 subfamily F member 2) This gene 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. The enzyme starts the process of inactivating and degrading leukotriene B4, a potent mediator of inflammation. This gene is part of a cluster of cytochrome P450 genes on chromosome 19. Another member of this family, CYP4F11, is approximately 16 kb away. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.22758538).
• BS2: High AC in GnomAd4 at 17 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001082.5. 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
	CYP4F2	NM_001082.5	MANE Select	c.1093C>T	p.Arg365Cys	missense	Exon 9 of 13	NP_001073.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP4F2	ENST00000221700.11	TSL:1 MANE Select	c.1093C>T	p.Arg365Cys	missense	Exon 9 of 13	ENSP00000221700.3	P78329-1
	CYP4F2	ENST00000011989.11	TSL:1	c.1093C>T	p.Arg365Cys	missense	Exon 9 of 13	ENSP00000011989.8	A0A0A0MQR0
	CYP4F2	ENST00000886782.1		c.1189C>T	p.Arg397Cys	missense	Exon 10 of 14	ENSP00000556841.1

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 152144 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000358 AC: 9 AN: 251368 AF XY: 0.0000515

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000294 AC: 43 AN: 1461662 Hom.: 0 Cov.: 30 AF XY: 0.0000330 AC XY: 24 AN XY: 727156

African (AFR) AF: 0.000149 AC: 5 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39670

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.0000216 AC: 24 AN: 1111890

Other (OTH) AF: 0.0000497 AC: 3 AN: 60382

GnomAD4 genome AF: 0.000112 AC: 17 AN: 152262 Hom.: 0 Cov.: 31 AF XY: 0.000175 AC XY: 13 AN XY: 74454

African (AFR) AF: 0.000241 AC: 10 AN: 41556

American (AMR) AF: 0.00 AC: 0 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5162

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68016

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000718

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000412 AC: 5

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions as Germline

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	0.11
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.68	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		1.0
PrimateAI	Benign	0.32	T
PROVEAN	Pathogenic	-6.6	D
REVEL	Benign	0.18
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.028	D
Polyphen		0.69	P
Vest4		0.44
MVP		0.63
MPC		0.41
ClinPred		0.27	T
GERP RS		1.6
PromoterAI		-0.031	Neutral
Varity_R		0.47
gMVP		0.58
Mutation Taster		=71/29	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs200373927; hg19: chr19-15996756;