dbSNP rs28391521: APOL1:c.315-136A>G (chr22-36265015-A-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_003661.4(APOL1):c.315-136A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.824 in 1,138,988 control chromosomes in the GnomAD database, including 388,049 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.86 ( 56192 hom., cov: 28)

Exomes 𝑓: 0.82 ( 331857 hom. )

Consequence

APOL1
NM_003661.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.76

Publications

3 publications found

Variant links:

Genes affected

APOL1 (HGNC:618): (apolipoprotein L1) This gene encodes a secreted high density lipoprotein which binds to apolipoprotein A-I. Apolipoprotein A-I is a relatively abundant plasma protein and is the major apoprotein of HDL. It is involved in the formation of most cholesteryl esters in plasma and also promotes efflux of cholesterol from cells. This apolipoprotein L family member may play a role in lipid exchange and transport throughout the body, as well as in reverse cholesterol transport from peripheral cells to the liver. Several different transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2008]

APOL1 Gene-Disease associations (from GenCC):

focal segmental glomerulosclerosis 4, susceptibility to
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

APOL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.03).

BP6

Variant 22-36265015-A-G is Benign according to our data. Variant chr22-36265015-A-G is described in ClinVar as [Benign]. Clinvar id is 1183411.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.944 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOL1	NM_003661.4 link	c.315-136A>G		intron_variant	Intron 5 of 5	ENST00000397278.8	NP_003652.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOL1	ENST00000397278.8 link	c.315-136A>G		intron_variant	Intron 5 of 5	1	NM_003661.4	ENSP00000380448.4		O14791-1

Frequencies

GnomAD3 genomes

AF:

0.857

AC:

130163

AN:

151826

Hom.:

56138

Cov.:

show subpopulations

Gnomad AFR

AF:

0.952

Gnomad AMI

AF:

0.796

Gnomad AMR

AF:

0.873

Gnomad ASJ

AF:

0.819

Gnomad EAS

AF:

0.844

Gnomad SAS

AF:

0.842

Gnomad FIN

AF:

0.844

Gnomad MID

AF:

0.823

Gnomad NFE

AF:

0.804

Gnomad OTH

AF:

0.835

GnomAD4 exome

AF:

0.819

AC:

808381

AN:

987044

Hom.:

331857

AF XY:

0.819

AC XY:

404829

AN XY:

494586

show subpopulations

African (AFR)

AF:

0.957

AC:

21127

AN:

22086

American (AMR)

AF:

0.893

AC:

19434

AN:

21758

Ashkenazi Jewish (ASJ)

AF:

0.832

AC:

14294

AN:

17176

East Asian (EAS)

AF:

0.843

AC:

28462

AN:

33754

South Asian (SAS)

AF:

0.834

AC:

48731

AN:

58398

European-Finnish (FIN)

AF:

0.843

AC:

38521

AN:

45670

Middle Eastern (MID)

AF:

0.772

AC:

2336

AN:

3024

European-Non Finnish (NFE)

AF:

0.808

AC:

599829

AN:

741990

Other (OTH)

AF:

0.825

AC:

35647

AN:

43188

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

6791

13582

20373

27164

33955

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.857

AC:

130275

AN:

151944

Hom.:

56192

Cov.:

AF XY:

0.860

AC XY:

63897

AN XY:

74272

show subpopulations

African (AFR)

AF:

0.952

AC:

39456

AN:

41448

American (AMR)

AF:

0.873

AC:

13342

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.819

AC:

2844

AN:

3472

East Asian (EAS)

AF:

0.844

AC:

4345

AN:

5150

South Asian (SAS)

AF:

0.842

AC:

4040

AN:

4800

European-Finnish (FIN)

AF:

0.844

AC:

8910

AN:

10562

Middle Eastern (MID)

AF:

0.823

AC:

242

AN:

294

European-Non Finnish (NFE)

AF:

0.804

AC:

54607

AN:

67922

Other (OTH)

AF:

0.836

AC:

1763

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

905

1810

2716

3621

4526

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.902

Hom.:

12771

Bravo

AF:

0.865

Asia WGS

AF:

0.852

AC:

2961

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.1

(source)

DANN

Benign

0.59

PhyloP100

-2.8

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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rs28391521

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over