19-15878920-T-C

Variant names:

• chr19-15878920-T-C
• rs4020346
• NM_001082.5:c.1414A>G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Strong BP6

The NM_001082.5(CYP4F2):​c.1414A>G​(p.Thr472Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.17 (4 hom.)
  • Failed GnomAD Quality Control
• Consequence: CYP4F2 NM_001082.5 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.149

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

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011447012).
• BP6: Variant 19-15878920-T-C is Benign according to our data. Variant chr19-15878920-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3059292.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP4F2	NM_001082.5	c.1414A>G	p.Thr472Ala	missense_variant	Exon 13 of 13	ENST00000221700.11	NP_001073.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP4F2	ENST00000221700.11	c.1414A>G	p.Thr472Ala	missense_variant	Exon 13 of 13	1	NM_001082.5	ENSP00000221700.3
CYP4F2	ENST00000011989.11	c.1414A>G	p.Thr472Ala	missense_variant	Exon 13 of 13	1		ENSP00000011989.8
CYP4F2	ENST00000589654.2	c.201A>G	p.Arg67Arg	synonymous_variant	Exon 3 of 3	3		ENSP00000467846.1
CYP4F2	ENST00000392846.7	n.1357A>G		non_coding_transcript_exon_variant	Exon 11 of 11	2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 3416 AN: 103230 Hom.: 0 Cov.: 33 FAILED QC

Gnomad AFR AF: 0.0466

Gnomad AMI AF: 0.0144

Gnomad AMR AF: 0.0374

Gnomad ASJ AF: 0.0170

Gnomad EAS AF: 0.0373

Gnomad SAS AF: 0.0160

Gnomad FIN AF: 0.0506

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.0246

Gnomad OTH AF: 0.0303

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.167 AC: 147828 AN: 887088 Hom.: 4 Cov.: 81 AF XY: 0.157 AC XY: 70028 AN XY: 444656

Gnomad4 AFR exome AF: 0.229

Gnomad4 AMR exome AF: 0.176

Gnomad4 ASJ exome AF: 0.0820

Gnomad4 EAS exome AF: 0.0885

Gnomad4 SAS exome AF: 0.0638

Gnomad4 FIN exome AF: 0.136

Gnomad4 NFE exome AF: 0.183

Gnomad4 OTH exome AF: 0.133

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0331 AC: 3419 AN: 103298 Hom.: 0 Cov.: 33 AF XY: 0.0383 AC XY: 1904 AN XY: 49714

Gnomad4 AFR AF: 0.0465

Gnomad4 AMR AF: 0.0375

Gnomad4 ASJ AF: 0.0170

Gnomad4 EAS AF: 0.0374

Gnomad4 SAS AF: 0.0161

Gnomad4 FIN AF: 0.0506

Gnomad4 NFE AF: 0.0246

Gnomad4 OTH AF: 0.0300

Alfa AF: 0.165 Hom.: 0

ExAC AF: 0.349 AC: 42415

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

CYP4F2-related disorder Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.30
DANN	Benign	0.35
DEOGEN2	Benign	0.052	T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.25	T;T
MetaRNN	Benign	0.011	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-2.1	N;.
REVEL	Benign	0.12
Sift	Benign	0.41	T;.
Sift4G	Benign	0.33	T;T
Polyphen		0.0	B;.
Vest4		0.030
MPC		0.15
ClinPred		0.0020	T
GERP RS		0.20
Varity_R		0.058
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4020346; hg19: chr19-15989730; COSMIC: COSV55616098; COSMIC: COSV55616098;