Genetic Variant ENST00000361710.6:c.-498-663G>A (chr22-36161452-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000361710.6(APOL3):c.-498-663G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 165,378 control chromosomes in the GnomAD database, including 12,998 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 0.34 ( 11512 hom., cov: 32)

Exomes 𝑓: 0.45 ( 1486 hom. )

Consequence

APOL3
ENST00000361710.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.835

Publications

2 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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOL3	NM_145641.3 link	c.-499+32G>A		intron_variant	Intron 2 of 4		NP_663616.1
APOL3	NM_145642.3 link	c.-498-663G>A		intron_variant	Intron 1 of 3		NP_663617.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOL3	ENST00000361710.6 link	c.-498-663G>A		intron_variant	Intron 1 of 3	1		ENSP00000355164.2
APOL3	ENST00000397287.6 link	c.-499+32G>A		intron_variant	Intron 2 of 4	1		ENSP00000380456.2

Frequencies

GnomAD3 genomes

AF:

0.344

AC:

52286

AN:

152016

Hom.:

11493

Cov.:

show subpopulations

Gnomad AFR

AF:

0.108

Gnomad AMI

AF:

0.330

Gnomad AMR

AF:

0.549

Gnomad ASJ

AF:

0.422

Gnomad EAS

AF:

0.833

Gnomad SAS

AF:

0.540

Gnomad FIN

AF:

0.433

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.370

Gnomad OTH

AF:

0.391

GnomAD4 exome

AF:

0.449

AC:

5946

AN:

13244

Hom.:

1486

Cov.:

AF XY:

0.450

AC XY:

3121

AN XY:

6932

show subpopulations

African (AFR)

AF:

0.0762

AC:

AN:

210

American (AMR)

AF:

0.597

AC:

1401

AN:

2348

Ashkenazi Jewish (ASJ)

AF:

0.439

AC:

AN:

164

East Asian (EAS)

AF:

0.839

AC:

547

AN:

652

South Asian (SAS)

AF:

0.507

AC:

865

AN:

1706

European-Finnish (FIN)

AF:

0.381

AC:

102

AN:

268

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.369

AC:

2688

AN:

7292

Other (OTH)

AF:

0.420

AC:

248

AN:

590

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

137

274

410

547

684

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

164

246

328

410

<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:

0.344

AC:

52315

AN:

152134

Hom.:

11512

Cov.:

AF XY:

0.357

AC XY:

26572

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.108

AC:

4469

AN:

41498

American (AMR)

AF:

0.550

AC:

8411

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.422

AC:

1464

AN:

3472

East Asian (EAS)

AF:

0.833

AC:

4316

AN:

5184

South Asian (SAS)

AF:

0.541

AC:

2605

AN:

4818

European-Finnish (FIN)

AF:

0.433

AC:

4582

AN:

10584

Middle Eastern (MID)

AF:

0.497

AC:

146

AN:

294

European-Non Finnish (NFE)

AF:

0.370

AC:

25182

AN:

67968

Other (OTH)

AF:

0.397

AC:

840

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1561

3122

4682

6243

7804

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

512

1024

1536

2048

2560

<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:

0.206

Hom.:

534

Bravo

AF:

0.342

Asia WGS

AF:

0.661

AC:

2294

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.042

(source)

DANN

Benign

0.28

PhyloP100

-0.83

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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