NM_001082.5:c.554G>T

Variant names:

• chr19-15890405-C-A
• rs3093153
• NM_001082.5:c.554G>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001082.5(CYP4F2):​c.554G>T​(p.Gly185Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0484 in 1,613,994 control chromosomes in the GnomAD database, including 2,286 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.049 (199 hom., cov: 32)
  • Exomes 𝑓: 0.048 (2087 hom.)
• Consequence: CYP4F2 NM_001082.5 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.75
• Publications: 30 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0025855303).
• BP6: Variant 19-15890405-C-A is Benign according to our data. Variant chr19-15890405-C-A is described in ClinVar as Benign. ClinVar VariationId is 3055377.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0583 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP4F2	NM_001082.5	MANE Select	c.554G>T	p.Gly185Val	missense	Exon 6 of 13	NP_001073.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP4F2	ENST00000221700.11	TSL:1 MANE Select	c.554G>T	p.Gly185Val	missense	Exon 6 of 13	ENSP00000221700.3
	CYP4F2	ENST00000011989.11	TSL:1	c.554G>T	p.Gly185Val	missense	Exon 6 of 13	ENSP00000011989.8
	CYP4F2	ENST00000886782.1		c.650G>T	p.Gly217Val	missense	Exon 7 of 14	ENSP00000556841.1

Frequencies

GnomAD3 genomes AF: 0.0490 AC: 7452 AN: 152142 Hom.: 197 Cov.: 32

Gnomad AFR AF: 0.0332

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.0408

Gnomad ASJ AF: 0.0404

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00455

Gnomad FIN AF: 0.0980

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0599

Gnomad OTH AF: 0.0482

GnomAD2 exomes AF: 0.0461 AC: 11595 AN: 251462 AF XY: 0.0458

Gnomad AFR exome AF: 0.0328

Gnomad AMR exome AF: 0.0277

Gnomad ASJ exome AF: 0.0437

Gnomad EAS exome AF: 0.000326

Gnomad FIN exome AF: 0.0975

Gnomad NFE exome AF: 0.0616

Gnomad OTH exome AF: 0.0535

GnomAD4 exome AF: 0.0483 AC: 70591 AN: 1461734 Hom.: 2087 Cov.: 31 AF XY: 0.0477 AC XY: 34684 AN XY: 727178

African (AFR) AF: 0.0308 AC: 1030 AN: 33476

American (AMR) AF: 0.0290 AC: 1297 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0413 AC: 1079 AN: 26132

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39654

South Asian (SAS) AF: 0.00759 AC: 655 AN: 86254

European-Finnish (FIN) AF: 0.100 AC: 5349 AN: 53406

Middle Eastern (MID) AF: 0.0293 AC: 169 AN: 5766

European-Non Finnish (NFE) AF: 0.0526 AC: 58459 AN: 1111946

Other (OTH) AF: 0.0421 AC: 2544 AN: 60382

GnomAD4 genome AF: 0.0490 AC: 7467 AN: 152260 Hom.: 199 Cov.: 32 AF XY: 0.0488 AC XY: 3630 AN XY: 74458

African (AFR) AF: 0.0335 AC: 1394 AN: 41564

American (AMR) AF: 0.0408 AC: 624 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0404 AC: 140 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5174

South Asian (SAS) AF: 0.00477 AC: 23 AN: 4826

European-Finnish (FIN) AF: 0.0980 AC: 1039 AN: 10598

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0599 AC: 4072 AN: 68004

Other (OTH) AF: 0.0473 AC: 100 AN: 2116

Alfa AF: 0.0529 Hom.: 532

Bravo AF: 0.0449

TwinsUK AF: 0.0553 AC: 205

ALSPAC AF: 0.0493 AC: 190

ESP6500AA AF: 0.0297 AC: 131

ESP6500EA AF: 0.0594 AC: 511

ExAC AF: 0.0471 AC: 5723

Asia WGS AF: 0.00982 AC: 34 AN: 3478

EpiCase AF: 0.0601

EpiControl AF: 0.0583

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	CYP4F2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.26	T
Eigen	Benign	0.027
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.55	D
LIST_S2	Uncertain	0.95	D
MetaRNN	Benign	0.0026	T
MetaSVM	Benign	-0.62	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		2.8
PrimateAI	Benign	0.32	T
PROVEAN	Pathogenic	-6.5	D
REVEL	Benign	0.21
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.014	D
Polyphen		0.92	P
Vest4		0.22
MPC		0.41
ClinPred		0.086	T
GERP RS		3.1
Varity_R		0.76
gMVP		0.54
Mutation Taster		=86/14	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs3093153; hg19: chr19-16001215;