rs2239785

Positions:

Variant summary

Our verdict is Benign. Variant got -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. 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 same amino acid change has been previously reported as Likely benignin UniProt.

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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 1168875.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36265284-G-A is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
APOL1	NM_003661.4 linkuse as main transcript	c.448G>A	p.Glu150Lys	missense_variant	6/6	ENST00000397278.8	NP_003652.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOL1	ENST00000397278.8 linkuse as main transcript	c.448G>A	p.Glu150Lys	missense_variant	6/6	1	NM_003661.4	ENSP00000380448	A2	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

GnomAD3 exomes

AF:

0.791

AC:

198800

AN:

251180

Hom.:

80607

AF XY:

0.797

AC XY:

108255

AN XY:

135778

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 SAS exome

AF:

0.815

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

Gnomad4 AFR exome

AF:

0.348

Gnomad4 AMR exome

AF:

0.874

Gnomad4 ASJ exome

AF:

0.821

Gnomad4 EAS exome

AF:

0.833

Gnomad4 SAS exome

AF:

0.816

Gnomad4 FIN exome

AF:

0.842

Gnomad4 NFE exome

AF:

0.807

Gnomad4 OTH exome

AF:

0.782

GnomAD4 genome

AF:

0.685

AC:

104116

AN:

152068

Hom.:

38824

Cov.:

AF XY:

0.694

AC XY:

51587

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.360

Gnomad4 AMR

AF:

0.816

Gnomad4 ASJ

AF:

0.812

Gnomad4 EAS

AF:

0.824

Gnomad4 SAS

AF:

0.823

Gnomad4 FIN

AF:

0.842

Gnomad4 NFE

AF:

0.799

Gnomad4 OTH

AF:

0.723

Alfa

AF:

0.778

Hom.:

90634

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	This variant is associated with the following publications: (PMID: 19239905, 22239288) -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jul 15, 2024

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

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

MutationTaster

Benign

1.0

P;P;P;P;P;P;P

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

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

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