dbSNP rs2074900: CYP4F2:p.His343His (chr19-15886010-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001082.5(CYP4F2):c.1029C>T(p.His343His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 1,613,564 control chromosomes in the GnomAD database, including 75,671 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.27 ( 5765 hom., cov: 30)

Exomes 𝑓: 0.31 ( 69906 hom. )

Consequence

CYP4F2
NM_001082.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.08

Publications

32 publications found

Variant links:

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]

CYP4F2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.015).

BP6

Variant 19-15886010-G-A is Benign according to our data. Variant chr19-15886010-G-A is described in ClinVar as Benign. ClinVar VariationId is 3056285.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP4F2	NM_001082.5 link	c.1029C>T	p.His343His	synonymous_variant	Exon 9 of 13	ENST00000221700.11	NP_001073.3	P78329-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP4F2	ENST00000221700.11 link	c.1029C>T	p.His343His	synonymous_variant	Exon 9 of 13	1	NM_001082.5	ENSP00000221700.3		P78329-1

Frequencies

GnomAD3 genomes

AF:

0.268

AC:

40703

AN:

151844

Hom.:

5769

Cov.:

show subpopulations

Gnomad AFR

AF:

0.186

Gnomad AMI

AF:

0.298

Gnomad AMR

AF:

0.262

Gnomad ASJ

AF:

0.253

Gnomad EAS

AF:

0.232

Gnomad SAS

AF:

0.264

Gnomad FIN

AF:

0.295

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.319

Gnomad OTH

AF:

0.259

GnomAD2 exomes

AF:

0.283

AC:

70998

AN:

251290

AF XY:

0.284

show subpopulations

Gnomad AFR exome

AF:

0.182

Gnomad AMR exome

AF:

0.251

Gnomad ASJ exome

AF:

0.253

Gnomad EAS exome

AF:

0.245

Gnomad FIN exome

AF:

0.299

Gnomad NFE exome

AF:

0.318

Gnomad OTH exome

AF:

0.276

GnomAD4 exome

AF:

0.306

AC:

446849

AN:

1461602

Hom.:

69906

Cov.:

AF XY:

0.304

AC XY:

221366

AN XY:

727096

show subpopulations

African (AFR)

AF:

0.183

AC:

6125

AN:

33478

American (AMR)

AF:

0.255

AC:

11408

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

6532

AN:

26128

East Asian (EAS)

AF:

0.205

AC:

8142

AN:

39680

South Asian (SAS)

AF:

0.262

AC:

22621

AN:

86228

European-Finnish (FIN)

AF:

0.306

AC:

16352

AN:

53398

Middle Eastern (MID)

AF:

0.215

AC:

1237

AN:

5758

European-Non Finnish (NFE)

AF:

0.321

AC:

356790

AN:

1111854

Other (OTH)

AF:

0.292

AC:

17642

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

20389

40779

61168

81558

101947

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11536

23072

34608

46144

57680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.268

AC:

40693

AN:

151962

Hom.:

5765

Cov.:

AF XY:

0.265

AC XY:

19659

AN XY:

74262

show subpopulations

African (AFR)

AF:

0.185

AC:

7684

AN:

41460

American (AMR)

AF:

0.261

AC:

3992

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.253

AC:

878

AN:

3470

East Asian (EAS)

AF:

0.232

AC:

1195

AN:

5156

South Asian (SAS)

AF:

0.264

AC:

1270

AN:

4808

European-Finnish (FIN)

AF:

0.295

AC:

3110

AN:

10544

Middle Eastern (MID)

AF:

0.167

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.319

AC:

21703

AN:

67942

Other (OTH)

AF:

0.256

AC:

541

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1487

2974

4461

5948

7435

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

412

824

1236

1648

2060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.290

Hom.:

2860

Bravo

AF:

0.259

Asia WGS

AF:

0.226

AC:

789

AN:

3478

EpiCase

AF:

0.301

EpiControl

AF:

0.298

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CYP4F2-related disorder

Benign:1

Oct 18, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as 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

BayesDel_noAF

Benign

-0.65

CADD

Benign

8.8

(source)

DANN

Uncertain

0.99

PhyloP100

2.1

PromoterAI

0.0052

Neutral

(source)

Mutation Taster

=93/7

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over