rs16996616

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 777703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36265845-G-A is described in Lovd as [Benign].

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		O14791-1

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

GnomAD3 exomes

AF:

0.00764

AC:

1921

AN:

251428

Hom.:

AF XY:

0.00623

AC XY:

846

AN XY:

135902

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 SAS exome

AF:

0.00412

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

Gnomad4 AFR exome

AF:

0.0888

Gnomad4 AMR exome

AF:

0.00568

Gnomad4 ASJ exome

AF:

0.000574

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00414

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000593

Gnomad4 OTH exome

AF:

0.00806

GnomAD4 genome

AF:

0.0258

AC:

3929

AN:

152262

Hom.:

163

Cov.:

AF XY:

0.0253

AC XY:

1883

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0878

Gnomad4 AMR

AF:

0.0102

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000911

Gnomad4 OTH

AF:

0.0166

Alfa

AF:

0.00645

Hom.:

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

- -

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

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

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over