Genetic Variant NM_145639.2:c.-88+3536T>C (chr22-36157133-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_145639.2(APOL3):c.-88+3536T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 412,220 control chromosomes in the GnomAD database, including 32,616 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 0.30 ( 9383 hom., cov: 32)

Exomes 𝑓: 0.40 ( 23233 hom. )

Consequence

APOL3
NM_145639.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.123

Publications

4 publications found

Variant links:

Genes affected

APOL3 (HGNC:14868): (apolipoprotein L3) This gene is a member of the apolipoprotein L gene family, and it is present in a cluster with other family members on chromosome 22. The encoded protein is found in the cytoplasm, where it may affect the movement of lipids, including cholesterol, and/or allow the binding of lipids to organelles. In addition, expression of this gene is up-regulated by tumor necrosis factor-alpha in endothelial cells lining the normal and atherosclerotic iliac artery and aorta. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2015]

APOL3 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=-0.72).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145639.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
APOL3	NM_145639.2	MANE Select	c.-88+3536T>C	intron	N/A	NP_663614.1
APOL3	NM_145640.2		c.223+3536T>C	intron	N/A	NP_663615.1
APOL3	NM_001393587.1		c.-317+2244T>C	intron	N/A	NP_001380516.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
APOL3	ENST00000424878.4	TSL:1 MANE Select	c.-88+3536T>C	intron	N/A	ENSP00000415779.3
APOL3	ENST00000349314.7	TSL:1	c.223+3536T>C	intron	N/A	ENSP00000344577.2
APOL3	ENST00000361710.6	TSL:1	c.-378+3536T>C	intron	N/A	ENSP00000355164.2

Frequencies

GnomAD3 genomes

AF:

0.301

AC:

45697

AN:

151974

Hom.:

9369

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0722

Gnomad AMI

AF:

0.308

Gnomad AMR

AF:

0.501

Gnomad ASJ

AF:

0.356

Gnomad EAS

AF:

0.843

Gnomad SAS

AF:

0.517

Gnomad FIN

AF:

0.389

Gnomad MID

AF:

0.402

Gnomad NFE

AF:

0.320

Gnomad OTH

AF:

0.339

GnomAD4 exome

AF:

0.396

AC:

102939

AN:

260128

Hom.:

23233

AF XY:

0.406

AC XY:

59824

AN XY:

147520

show subpopulations

African (AFR)

AF:

0.0656

AC:

412

AN:

6280

American (AMR)

AF:

0.634

AC:

11880

AN:

18746

Ashkenazi Jewish (ASJ)

AF:

0.360

AC:

3225

AN:

8954

East Asian (EAS)

AF:

0.851

AC:

7411

AN:

8712

South Asian (SAS)

AF:

0.497

AC:

26870

AN:

54040

European-Finnish (FIN)

AF:

0.362

AC:

4039

AN:

11170

Middle Eastern (MID)

AF:

0.339

AC:

869

AN:

2562

European-Non Finnish (NFE)

AF:

0.319

AC:

43935

AN:

137684

Other (OTH)

AF:

0.359

AC:

4298

AN:

11980

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

2732

5464

8197

10929

13661

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

410

820

1230

1640

2050

<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:

0.301

AC:

45717

AN:

152092

Hom.:

9383

Cov.:

AF XY:

0.315

AC XY:

23450

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.0721

AC:

2992

AN:

41520

American (AMR)

AF:

0.502

AC:

7665

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.356

AC:

1235

AN:

3472

East Asian (EAS)

AF:

0.843

AC:

4360

AN:

5172

South Asian (SAS)

AF:

0.518

AC:

2489

AN:

4808

European-Finnish (FIN)

AF:

0.389

AC:

4113

AN:

10572

Middle Eastern (MID)

AF:

0.405

AC:

119

AN:

294

European-Non Finnish (NFE)

AF:

0.320

AC:

21739

AN:

67970

Other (OTH)

AF:

0.345

AC:

725

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1404

2808

4211

5615

7019

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

464

928

1392

1856

2320

<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:

0.330

Hom.:

7432

Bravo

AF:

0.300

Asia WGS

AF:

0.628

AC:

2177

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

6.4

(source)

DANN

Benign

0.89

PhyloP100

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over