Genetic Variant APOL1:c.-20+537C>T (chr22-36253756-C-T) – 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_003661.4(APOL1):c.-20+537C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 599,592 control chromosomes in the GnomAD database, including 9,998 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2018 hom., cov: 32)

Exomes 𝑓: 0.18 ( 7980 hom. )

Consequence

APOL1
NM_003661.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.30

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 (BayesDel_noAF=-0.89).

BP6

Variant 22-36253756-C-T is Benign according to our data. Variant chr22-36253756-C-T is described in ClinVar as [Benign]. Clinvar id is 1255247.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOL1	NM_003661.4 link	c.-20+537C>T		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.-20+537C>T		intron_variant	Intron 1 of 5	1	NM_003661.4	ENSP00000380448.4		O14791-1

Frequencies

GnomAD3 genomes

AF:

0.147

AC:

22307

AN:

152060

Hom.:

2019

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0470

Gnomad AMI

AF:

0.202

Gnomad AMR

AF:

0.126

Gnomad ASJ

AF:

0.233

Gnomad EAS

AF:

0.145

Gnomad SAS

AF:

0.158

Gnomad FIN

AF:

0.153

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.204

Gnomad OTH

AF:

0.171

GnomAD4 exome

AF:

0.182

AC:

81531

AN:

447414

Hom.:

7980

AF XY:

0.182

AC XY:

42967

AN XY:

235638

show subpopulations

Gnomad4 AFR exome

AF:

0.0454

Gnomad4 AMR exome

AF:

0.109

Gnomad4 ASJ exome

AF:

0.225

Gnomad4 EAS exome

AF:

0.133

Gnomad4 SAS exome

AF:

0.157

Gnomad4 FIN exome

AF:

0.148

Gnomad4 NFE exome

AF:

0.205

Gnomad4 OTH exome

AF:

0.179

GnomAD4 genome

AF:

0.147

AC:

22305

AN:

152178

Hom.:

2018

Cov.:

AF XY:

0.143

AC XY:

10619

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.0470

Gnomad4 AMR

AF:

0.126

Gnomad4 ASJ

AF:

0.233

Gnomad4 EAS

AF:

0.145

Gnomad4 SAS

AF:

0.159

Gnomad4 FIN

AF:

0.153

Gnomad4 NFE

AF:

0.204

Gnomad4 OTH

AF:

0.172

Alfa

AF:

0.161

Hom.:

270

Bravo

AF:

0.140

Asia WGS

AF:

0.141

AC:

489

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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

- -

Aug 20, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.40

DANN

Benign

0.50

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