rs16996616

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.1009G>A(p.Asp337Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00543 in 1,614,154 control chromosomes in the GnomAD database, including 329 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D337G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.026 ( 163 hom., cov: 31)

Exomes 𝑓: 0.0033 ( 166 hom. )

Consequence

APOL1
NM_003661.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.205

Publications

24 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=0.0029411316).

BP6

Variant 22-36265845-G-A is Benign according to our data. Variant chr22-36265845-G-A is described in ClinVar as Benign. ClinVar VariationId is 777703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOL1	NM_003661.4 link	c.1009G>A	p.Asp337Asn	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.1009G>A	p.Asp337Asn	missense_variant	Exon 6 of 6	1	NM_003661.4	ENSP00000380448.4

Frequencies

GnomAD3 genomes

AF:

0.0258

AC:

3918

AN:

152144

Hom.:

162

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0877

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0103

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00353

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.000911

Gnomad OTH

AF:

0.0167

GnomAD2 exomes

AF:

0.00764

AC:

1921

AN:

251428

AF XY:

0.00623

show subpopulations

Gnomad AFR exome

AF:

0.0914

Gnomad AMR exome

AF:

0.00503

Gnomad ASJ exome

AF:

0.00109

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000897

Gnomad OTH exome

AF:

0.00391

GnomAD4 exome

AF:

0.00330

AC:

4831

AN:

1461892

Hom.:

166

Cov.:

AF XY:

0.00304

AC XY:

2209

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.0888

AC:

2972

AN:

33478

American (AMR)

AF:

0.00568

AC:

254

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000574

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00414

AC:

357

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.0151

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000593

AC:

659

AN:

1112012

Other (OTH)

AF:

0.00806

AC:

487

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

275

551

826

1102

1377

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

220

330

440

550

<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:

0.0258

AC:

3929

AN:

152262

Hom.:

163

Cov.:

AF XY:

0.0253

AC XY:

1883

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.0878

AC:

3646

AN:

41516

American (AMR)

AF:

0.0102

AC:

156

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00311

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000911

AC:

AN:

68036

Other (OTH)

AF:

0.0166

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

183

366

550

733

916

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<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:

0.0112

Hom.:

138

Bravo

AF:

0.0296

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0844

AC:

372

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.00908

AC:

1103

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.00109

EpiControl

AF:

0.00113

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jan 24, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 02, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.8

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.013

T;T;.;.;T

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.74

.;.;T;T;T

MetaRNN

Benign

0.0029

T;T;T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

0.69

N;N;.;.;N

PhyloP100

0.20

PrimateAI

Benign

0.26

PROVEAN

Benign

0.72

N;N;N;N;N

REVEL

Benign

0.031

Sift

Benign

0.057

T;T;T;T;T

Sift4G

Benign

0.29

T;T;T;T;T

Polyphen

0.37

B;B;.;B;B

Vest4

0.038

MVP

0.38

MPC

0.14

ClinPred

0.0052

GERP RS

2.1

Varity_R

0.025

gMVP

0.16

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

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