Genetic Variant NM_000896.3:c.-2+142T>G (chr19-15641087-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000896.3(CYP4F3):c.-2+142T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 298,938 control chromosomes in the GnomAD database, including 21,324 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.36 ( 10124 hom., cov: 32)

Exomes 𝑓: 0.38 ( 11200 hom. )

Consequence

CYP4F3
NM_000896.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.762

Publications

9 publications found

Variant links:

Genes affected

CYP4F3 (HGNC:2646): (cytochrome P450 family 4 subfamily F member 3) This gene, CYP4F3, 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, CYP4F8, is approximately 18 kb away. Several transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Apr 2019]

CYP4F3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP4F3	NM_000896.3 link	c.-2+142T>G		intron_variant	Intron 1 of 12	ENST00000221307.13	NP_000887.2	Q08477-1A0A024R7J8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP4F3	ENST00000221307.13 link	c.-2+142T>G		intron_variant	Intron 1 of 12	1	NM_000896.3	ENSP00000221307.6		Q08477-1

Frequencies

GnomAD3 genomes

AF:

0.357

AC:

54227

AN:

151954

Hom.:

10129

Cov.:

show subpopulations

Gnomad AFR

AF:

0.283

Gnomad AMI

AF:

0.286

Gnomad AMR

AF:

0.332

Gnomad ASJ

AF:

0.378

Gnomad EAS

AF:

0.342

Gnomad SAS

AF:

0.400

Gnomad FIN

AF:

0.329

Gnomad MID

AF:

0.494

Gnomad NFE

AF:

0.408

Gnomad OTH

AF:

0.397

GnomAD4 exome

AF:

0.380

AC:

55744

AN:

146866

Hom.:

11200

AF XY:

0.382

AC XY:

29633

AN XY:

77584

show subpopulations

African (AFR)

AF:

0.283

AC:

1320

AN:

4660

American (AMR)

AF:

0.280

AC:

1647

AN:

5886

Ashkenazi Jewish (ASJ)

AF:

0.366

AC:

1523

AN:

4166

East Asian (EAS)

AF:

0.328

AC:

2299

AN:

7002

South Asian (SAS)

AF:

0.384

AC:

8058

AN:

20958

European-Finnish (FIN)

AF:

0.325

AC:

2250

AN:

6924

Middle Eastern (MID)

AF:

0.433

AC:

284

AN:

656

European-Non Finnish (NFE)

AF:

0.399

AC:

35262

AN:

88418

Other (OTH)

AF:

0.378

AC:

3101

AN:

8196

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

1590

3181

4771

6362

7952

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

246

492

738

984

1230

<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:

0.357

AC:

54233

AN:

152072

Hom.:

10124

Cov.:

AF XY:

0.354

AC XY:

26325

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.283

AC:

11734

AN:

41526

American (AMR)

AF:

0.332

AC:

5070

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.378

AC:

1310

AN:

3470

East Asian (EAS)

AF:

0.342

AC:

1766

AN:

5162

South Asian (SAS)

AF:

0.399

AC:

1925

AN:

4826

European-Finnish (FIN)

AF:

0.329

AC:

3479

AN:

10566

Middle Eastern (MID)

AF:

0.479

AC:

140

AN:

292

European-Non Finnish (NFE)

AF:

0.408

AC:

27709

AN:

67926

Other (OTH)

AF:

0.398

AC:

840

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1761

3523

5284

7046

8807

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

546

1092

1638

2184

2730

<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:

0.399

Hom.:

20010

Bravo

AF:

0.354

Asia WGS

AF:

0.393

AC:

1366

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.91

(source)

DANN

Benign

0.32

PhyloP100

-0.76

PromoterAI

-0.047

Neutral

(source)

Mutation Taster

=100/0

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

Computational scores

Splicing

Publications

Other links and lift over