rs2239785

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003661.4(APOL1):c.448G>A(p.Glu150Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.789 in 1,613,690 control chromosomes in the GnomAD database, including 510,429 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.68 ( 38824 hom., cov: 31)

Exomes 𝑓: 0.80 ( 471605 hom. )

Consequence

APOL1
NM_003661.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.258

Publications

81 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.4776589E-6).

BP6

Variant 22-36265284-G-A is Benign according to our data. Variant chr22-36265284-G-A is described in ClinVar as Benign. ClinVar VariationId is 1168875.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOL1	NM_003661.4 link	c.448G>A	p.Glu150Lys	missense_variant	Exon 6 of 6	ENST00000397278.8	NP_003652.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOL1	ENST00000397278.8 link	c.448G>A	p.Glu150Lys	missense_variant	Exon 6 of 6	1	NM_003661.4	ENSP00000380448.4		O14791-1

Frequencies

GnomAD3 genomes

AF:

0.685

AC:

104059

AN:

151950

Hom.:

38808

Cov.:

show subpopulations

Gnomad AFR

AF:

0.360

Gnomad AMI

AF:

0.764

Gnomad AMR

AF:

0.816

Gnomad ASJ

AF:

0.812

Gnomad EAS

AF:

0.824

Gnomad SAS

AF:

0.823

Gnomad FIN

AF:

0.842

Gnomad MID

AF:

0.759

Gnomad NFE

AF:

0.799

Gnomad OTH

AF:

0.721

GnomAD2 exomes

AF:

0.791

AC:

198800

AN:

251180

AF XY:

0.797

show subpopulations

Gnomad AFR exome

AF:

0.345

Gnomad AMR exome

AF:

0.881

Gnomad ASJ exome

AF:

0.818

Gnomad EAS exome

AF:

0.834

Gnomad FIN exome

AF:

0.840

Gnomad NFE exome

AF:

0.802

Gnomad OTH exome

AF:

0.805

GnomAD4 exome

AF:

0.800

AC:

1168760

AN:

1461622

Hom.:

471605

Cov.:

AF XY:

0.800

AC XY:

582048

AN XY:

727150

show subpopulations

African (AFR)

AF:

0.348

AC:

11626

AN:

33438

American (AMR)

AF:

0.874

AC:

39031

AN:

44652

Ashkenazi Jewish (ASJ)

AF:

0.821

AC:

21442

AN:

26122

East Asian (EAS)

AF:

0.833

AC:

33062

AN:

39700

South Asian (SAS)

AF:

0.816

AC:

70347

AN:

86236

European-Finnish (FIN)

AF:

0.842

AC:

45006

AN:

53420

Middle Eastern (MID)

AF:

0.729

AC:

4203

AN:

5768

European-Non Finnish (NFE)

AF:

0.807

AC:

896844

AN:

1111920

Other (OTH)

AF:

0.782

AC:

47199

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

14249

28498

42748

56997

71246

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20788

41576

62364

83152

103940

<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:

0.685

AC:

104116

AN:

152068

Hom.:

38824

Cov.:

AF XY:

0.694

AC XY:

51587

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.360

AC:

14933

AN:

41432

American (AMR)

AF:

0.816

AC:

12481

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.812

AC:

2818

AN:

3470

East Asian (EAS)

AF:

0.824

AC:

4261

AN:

5170

South Asian (SAS)

AF:

0.823

AC:

3963

AN:

4814

European-Finnish (FIN)

AF:

0.842

AC:

8917

AN:

10586

Middle Eastern (MID)

AF:

0.759

AC:

223

AN:

294

European-Non Finnish (NFE)

AF:

0.799

AC:

54296

AN:

67988

Other (OTH)

AF:

0.723

AC:

1527

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1356

2712

4067

5423

6779

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

804

1608

2412

3216

4020

<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:

0.765

Hom.:

176916

Bravo

AF:

0.669

TwinsUK

AF:

0.811

AC:

3006

ALSPAC

AF:

0.807

AC:

3109

ESP6500AA

AF:

0.374

AC:

1647

ESP6500EA

AF:

0.796

AC:

6844

ExAC

AF:

0.780

AC:

94686

Asia WGS

AF:

0.811

AC:

2817

AN:

3478

EpiCase

AF:

0.785

EpiControl

AF:

0.791

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 19239905, 22239288) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 99% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 92. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.018

T;T;.;.;.;T

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.0086

LIST_S2

Benign

0.76

.;.;T;T;T;T

MetaRNN

Benign

0.0000025

T;T;T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.1

L;L;.;.;.;L

PhyloP100

-0.26

PrimateAI

Benign

0.42

PROVEAN

Benign

-2.2

N;N;N;N;N;N

REVEL

Benign

0.031

Sift

Benign

0.43

T;T;T;T;T;T

Sift4G

Benign

0.39

T;T;T;T;T;T

Polyphen

0.99

D;D;.;D;.;D

Vest4

0.10

MPC

0.35

ClinPred

0.028

GERP RS

-2.2

Varity_R

0.035

gMVP

0.29

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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