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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000361710.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOL3	NM_145641.3		c.-499+32G>A		intron	N/A	NP_663616.1	O95236-3
	APOL3	NM_145642.3		c.-498-663G>A		intron	N/A	NP_663617.1	O95236-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOL3	ENST00000361710.6	TSL:1	c.-498-663G>A		intron	N/A	ENSP00000355164.2	O95236-3
	APOL3	ENST00000397287.6	TSL:1	c.-499+32G>A		intron	N/A	ENSP00000380456.2	O95236-3

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over