Genetic Variant APOL1:c.-19-27G>A (chr22-36254910-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001136540.2(APOL1):c.-46G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 1,612,258 control chromosomes in the GnomAD database, including 25,788 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1809 hom., cov: 32)

Exomes 𝑓: 0.18 ( 23979 hom. )

Consequence

APOL1
NM_001136540.2 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.312

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 (BayesDel_noAF=-1.01).

BP6

Variant 22-36254910-G-A is Benign according to our data. Variant chr22-36254910-G-A is described in ClinVar as [Benign]. Clinvar id is 1290711.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36254910-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOL1	NM_003661.4 link	c.-19-27G>A		intron_variant	Intron 1 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.-19-27G>A		intron_variant	Intron 1 of 5	1	NM_003661.4	ENSP00000380448.4		O14791-1

Frequencies

GnomAD3 genomes

AF:

0.141

AC:

21399

AN:

152076

Hom.:

1808

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0649

Gnomad AMI

AF:

0.0485

Gnomad AMR

AF:

0.124

Gnomad ASJ

AF:

0.169

Gnomad EAS

AF:

0.0470

Gnomad SAS

AF:

0.144

Gnomad FIN

AF:

0.185

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.191

Gnomad OTH

AF:

0.136

GnomAD3 exomes

AF:

0.150

AC:

37692

AN:

251352

Hom.:

3228

AF XY:

0.155

AC XY:

20998

AN XY:

135850

show subpopulations

Gnomad AFR exome

AF:

0.0653

Gnomad AMR exome

AF:

0.0942

Gnomad ASJ exome

AF:

0.166

Gnomad EAS exome

AF:

0.0378

Gnomad SAS exome

AF:

0.157

Gnomad FIN exome

AF:

0.177

Gnomad NFE exome

AF:

0.189

Gnomad OTH exome

AF:

0.155

GnomAD4 exome

AF:

0.176

AC:

257191

AN:

1460064

Hom.:

23979

Cov.:

AF XY:

0.177

AC XY:

128303

AN XY:

726434

show subpopulations

Gnomad4 AFR exome

AF:

0.0635

Gnomad4 AMR exome

AF:

0.0994

Gnomad4 ASJ exome

AF:

0.168

Gnomad4 EAS exome

AF:

0.0530

Gnomad4 SAS exome

AF:

0.159

Gnomad4 FIN exome

AF:

0.182

Gnomad4 NFE exome

AF:

0.189

Gnomad4 OTH exome

AF:

0.158

GnomAD4 genome

AF:

0.141

AC:

21405

AN:

152194

Hom.:

1809

Cov.:

AF XY:

0.142

AC XY:

10532

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0651

Gnomad4 AMR

AF:

0.124

Gnomad4 ASJ

AF:

0.169

Gnomad4 EAS

AF:

0.0472

Gnomad4 SAS

AF:

0.144

Gnomad4 FIN

AF:

0.185

Gnomad4 NFE

AF:

0.191

Gnomad4 OTH

AF:

0.133

Alfa

AF:

0.171

Hom.:

1134

Bravo

AF:

0.130

Asia WGS

AF:

0.0790

AC:

275

AN:

3478

EpiCase

AF:

0.185

EpiControl

AF:

0.189

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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 27% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 25. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.64

DANN

Benign

0.58

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