dbSNP rs2097465: APOL3:c.-88+4801G>A (chr22-36155868-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 NM_145639.2(APOL3):c.-88+4801G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 159,682 control chromosomes in the GnomAD database, including 5,912 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 0.25 ( 5612 hom., cov: 32)

Exomes 𝑓: 0.29 ( 300 hom. )

Consequence

APOL3
NM_145639.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.359

Publications

5 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=-1.03).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.335 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+4801G>A	intron	N/A	NP_663614.1
APOL3	NM_145640.2		c.223+4801G>A	intron	N/A	NP_663615.1
APOL3	NM_001393587.1		c.-317+3509G>A	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+4801G>A	intron	N/A	ENSP00000415779.3
APOL3	ENST00000349314.7	TSL:1	c.223+4801G>A	intron	N/A	ENSP00000344577.2
APOL3	ENST00000361710.6	TSL:1	c.-378+4801G>A	intron	N/A	ENSP00000355164.2

Frequencies

GnomAD3 genomes

AF:

0.252

AC:

38341

AN:

152036

Hom.:

5616

Cov.:

show subpopulations

Gnomad AFR

AF:

0.107

Gnomad AMI

AF:

0.321

Gnomad AMR

AF:

0.235

Gnomad ASJ

AF:

0.369

Gnomad EAS

AF:

0.107

Gnomad SAS

AF:

0.330

Gnomad FIN

AF:

0.269

Gnomad MID

AF:

0.309

Gnomad NFE

AF:

0.339

Gnomad OTH

AF:

0.282

GnomAD4 exome

AF:

0.289

AC:

2178

AN:

7528

Hom.:

300

Cov.:

AF XY:

0.295

AC XY:

1173

AN XY:

3980

show subpopulations

African (AFR)

AF:

0.196

AC:

AN:

112

American (AMR)

AF:

0.236

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.400

AC:

AN:

East Asian (EAS)

AF:

0.108

AC:

AN:

204

South Asian (SAS)

AF:

0.336

AC:

AN:

238

European-Finnish (FIN)

AF:

0.277

AC:

1031

AN:

3726

Middle Eastern (MID)

AF:

0.292

AC:

276

AN:

946

European-Non Finnish (NFE)

AF:

0.333

AC:

612

AN:

1838

Other (OTH)

AF:

0.280

AC:

AN:

322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

139

208

278

347

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.252

AC:

38348

AN:

152154

Hom.:

5612

Cov.:

AF XY:

0.250

AC XY:

18618

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.108

AC:

4470

AN:

41510

American (AMR)

AF:

0.235

AC:

3592

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.369

AC:

1281

AN:

3468

East Asian (EAS)

AF:

0.107

AC:

554

AN:

5176

South Asian (SAS)

AF:

0.329

AC:

1589

AN:

4826

European-Finnish (FIN)

AF:

0.269

AC:

2853

AN:

10596

Middle Eastern (MID)

AF:

0.291

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.339

AC:

23045

AN:

67978

Other (OTH)

AF:

0.279

AC:

587

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1453

2906

4360

5813

7266

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

426

852

1278

1704

2130

<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:

0.318

Hom.:

13552

Bravo

AF:

0.238

Asia WGS

AF:

0.186

AC:

651

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

2.3

(source)

DANN

Benign

0.63

PhyloP100

-0.36

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