Genetic Variant APOL3:c.-2095C>A (chr22-36166188-G-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_145641.3(APOL3):c.-2158C>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 151,986 control chromosomes in the GnomAD database, including 28,326 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 0.61 ( 28326 hom., cov: 31)

Exomes 𝑓: 0.75 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

APOL3
NM_145641.3 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.137

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=-0.93).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145641.3. 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.-2158C>A		upstream_gene	N/A	NP_663616.1	O95236-3
	APOL3	NM_145642.3		c.-2095C>A		upstream_gene	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.-2095C>A		upstream_gene	N/A	ENSP00000355164.2	O95236-3
	APOL3	ENST00000397287.6	TSL:1	c.-2158C>A		upstream_gene	N/A	ENSP00000380456.2	O95236-3

Frequencies

GnomAD3 genomes

AF:

0.605

AC:

91856

AN:

151868

Hom.:

28279

Cov.:

show subpopulations

Gnomad AFR

AF:

0.601

Gnomad AMI

AF:

0.450

Gnomad AMR

AF:

0.692

Gnomad ASJ

AF:

0.583

Gnomad EAS

AF:

0.863

Gnomad SAS

AF:

0.662

Gnomad FIN

AF:

0.684

Gnomad MID

AF:

0.646

Gnomad NFE

AF:

0.555

Gnomad OTH

AF:

0.612

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.750

AC:

AN:

Hom.:

Cov.:

AF XY:

0.750

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AF:

0.750

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.605

AC:

91960

AN:

151986

Hom.:

28326

Cov.:

AF XY:

0.613

AC XY:

45546

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.601

AC:

24895

AN:

41422

American (AMR)

AF:

0.692

AC:

10569

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.583

AC:

2020

AN:

3466

East Asian (EAS)

AF:

0.863

AC:

4463

AN:

5172

South Asian (SAS)

AF:

0.662

AC:

3194

AN:

4822

European-Finnish (FIN)

AF:

0.684

AC:

7216

AN:

10554

Middle Eastern (MID)

AF:

0.656

AC:

193

AN:

294

European-Non Finnish (NFE)

AF:

0.555

AC:

37703

AN:

67964

Other (OTH)

AF:

0.616

AC:

1297

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1853

3706

5560

7413

9266

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

760

1520

2280

3040

3800

<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:

0.581

Hom.:

10872

Bravo

AF:

0.605

Asia WGS

AF:

0.786

AC:

2729

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

1.5

(source)

DANN

Benign

0.29

PhyloP100

0.14

PromoterAI

-0.0042

Neutral

(source)

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over