dbSNP rs4301822: APOF:p.Ile311Thr (chr12-56361274-A-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_001638.4(APOF):c.932T>C(p.Ile311Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0308 in 1,613,896 control chromosomes in the GnomAD database, including 12,488 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.16 ( 6566 hom., cov: 32)

Exomes 𝑓: 0.017 ( 5922 hom. )

Consequence

APOF
NM_001638.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0160

Publications

11 publications found

Variant links:

Genes affected

APOF (HGNC:615): (apolipoprotein F) The product of this gene is one of the minor apolipoproteins found in plasma. This protein forms complexes with lipoproteins and may be involved in transport and/or esterification of cholesterol. [provided by RefSeq, Jul 2008]

APOF links:

ENSG00000307495 (HGNC:):

ENSG00000307495 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=4.9995535E-5).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOF	NM_001638.4 link	c.932T>C	p.Ile311Thr	missense_variant	Exon 2 of 2	ENST00000398189.4	NP_001629.1	Q13790

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOF	ENST00000398189.4 link	c.932T>C	p.Ile311Thr	missense_variant	Exon 2 of 2	1	NM_001638.4	ENSP00000381250.3		Q13790

Frequencies

GnomAD3 genomes

AF:

0.161

AC:

24436

AN:

152090

Hom.:

6532

Cov.:

show subpopulations

Gnomad AFR

AF:

0.554

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0673

Gnomad ASJ

AF:

0.0237

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00237

Gnomad OTH

AF:

0.107

GnomAD2 exomes

AF:

0.0421

AC:

10487

AN:

249188

AF XY:

0.0325

show subpopulations

Gnomad AFR exome

AF:

0.572

Gnomad AMR exome

AF:

0.0290

Gnomad ASJ exome

AF:

0.0229

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.00214

Gnomad OTH exome

AF:

0.0217

GnomAD4 exome

AF:

0.0173

AC:

25226

AN:

1461688

Hom.:

5922

Cov.:

AF XY:

0.0149

AC XY:

10842

AN XY:

727122

show subpopulations

African (AFR)

AF:

0.575

AC:

19236

AN:

33470

American (AMR)

AF:

0.0337

AC:

1507

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0215

AC:

561

AN:

26134

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00114

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0000562

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.0286

AC:

165

AN:

5768

European-Non Finnish (NFE)

AF:

0.00123

AC:

1372

AN:

1111864

Other (OTH)

AF:

0.0378

AC:

2283

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

810

1620

2430

3240

4050

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

468

936

1404

1872

2340

<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:

0.161

AC:

24524

AN:

152208

Hom.:

6566

Cov.:

AF XY:

0.156

AC XY:

11600

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.555

AC:

23011

AN:

41464

American (AMR)

AF:

0.0673

AC:

1029

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0237

AC:

AN:

3466

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.00187

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00237

AC:

161

AN:

68032

Other (OTH)

AF:

0.106

AC:

224

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

582

1164

1746

2328

2910

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

376

564

752

940

<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:

0.0621

Hom.:

6884

Bravo

AF:

0.184

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.540

AC:

2014

ESP6500EA

AF:

0.00453

AC:

ExAC

AF:

0.0504

AC:

6090

Asia WGS

AF:

0.0310

AC:

110

AN:

3478

EpiCase

AF:

0.00300

EpiControl

AF:

0.00379

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.57

CADD

Benign

8.1

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.045

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0064

LIST_S2

Benign

0.46

MetaRNN

Benign

0.000050

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.69

PhyloP100

-0.016

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.0

REVEL

Benign

0.020

Sift

Benign

0.068

Sift4G

Uncertain

0.026

Polyphen

0.014

Vest4

0.033

MPC

0.14

ClinPred

0.0084

GERP RS

-0.83

Varity_R

0.059

gMVP

0.12

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