Genetic Variant NM_145639.2: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:

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=-1.03).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOL3	NM_145639.2 link	c.-88+4801G>A		intron_variant	Intron 1 of 3	ENST00000424878.4	NP_663614.1	O95236-2A0A024R1G6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOL3	ENST00000424878.4 link	c.-88+4801G>A		intron_variant	Intron 1 of 3	1	NM_145639.2	ENSP00000415779.3		O95236-2

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over