dbSNP rs78739461: APOF:c.16+118T>G (chr12-56362612-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001638.4(APOF):c.16+118T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00898 in 1,011,424 control chromosomes in the GnomAD database, including 61 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 0.0079 ( 9 hom., cov: 32)

Exomes 𝑓: 0.0092 ( 52 hom. )

Consequence

APOF
NM_001638.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.02

Publications

1 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 (BayesDel_noAF=-0.74).

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00917 (7879/859336) while in subpopulation MID AF = 0.0196 (71/3630). AF 95% confidence interval is 0.0159. There are 52 homozygotes in GnomAdExome4. There are 4119 alleles in the male GnomAdExome4 subpopulation. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001638.4. 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
	APOF	NM_001638.4	MANE Select	c.16+118T>G		intron	N/A	NP_001629.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOF	ENST00000398189.4	TSL:1 MANE Select	c.16+118T>G		intron	N/A	ENSP00000381250.3
	ENSG00000307495	ENST00000826586.1		n.327+2046A>C		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00789

AC:

1199

AN:

151970

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00160

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.00964

Gnomad ASJ

AF:

0.0563

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00643

Gnomad FIN

AF:

0.00425

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00987

Gnomad OTH

AF:

0.0125

GnomAD4 exome

AF:

0.00917

AC:

7879

AN:

859336

Hom.:

AF XY:

0.00937

AC XY:

4119

AN XY:

439422

show subpopulations

African (AFR)

AF:

0.00225

AC:

AN:

20454

American (AMR)

AF:

0.00871

AC:

244

AN:

28006

Ashkenazi Jewish (ASJ)

AF:

0.0454

AC:

880

AN:

19376

East Asian (EAS)

AF:

0.0000878

AC:

AN:

34166

South Asian (SAS)

AF:

0.00645

AC:

404

AN:

62648

European-Finnish (FIN)

AF:

0.00519

AC:

250

AN:

48184

Middle Eastern (MID)

AF:

0.0196

AC:

AN:

3630

European-Non Finnish (NFE)

AF:

0.00909

AC:

5483

AN:

603470

Other (OTH)

AF:

0.0126

AC:

498

AN:

39402

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

382

764

1146

1528

1910

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

152

304

456

608

760

<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:

0.00788

AC:

1199

AN:

152088

Hom.:

Cov.:

AF XY:

0.00742

AC XY:

552

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.00159

AC:

AN:

41500

American (AMR)

AF:

0.00963

AC:

147

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.0563

AC:

195

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00644

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00425

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00989

AC:

672

AN:

67958

Other (OTH)

AF:

0.0123

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

120

181

241

301

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00823

Hom.:

Bravo

AF:

0.00830

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

(source)

DANN

Benign

0.82

PhyloP100

1.0

PromoterAI

0.048

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over