Variant chr22-36253745-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_003661.4(APOL1):c.-20+526G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0069 in 579,490 control chromosomes in the GnomAD database, including 82 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.016 ( 59 hom., cov: 32)

Exomes 𝑓: 0.0037 ( 23 hom. )

Consequence

APOL1
NM_003661.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.691

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 22-36253745-G-A is Benign according to our data. Variant chr22-36253745-G-A is described in ClinVar as [Benign]. Clinvar id is 1256906.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.016 (2432/152284) while in subpopulation AFR AF= 0.0512 (2125/41540). AF 95% confidence interval is 0.0493. There are 59 homozygotes in gnomad4. There are 1135 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 59 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOL1	NM_003661.4 linkuse as main transcript	c.-20+526G>A		intron_variant		ENST00000397278.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOL1	ENST00000397278.8 linkuse as main transcript	c.-20+526G>A		intron_variant		1	NM_003661.4	A2	O14791-1

Frequencies

GnomAD3 genomes

AF:

0.0159

AC:

2423

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0510

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00851

Gnomad ASJ

AF:

0.00691

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.00165

Gnomad OTH

AF:

0.0143

GnomAD4 exome

AF:

0.00366

AC:

1564

AN:

427206

Hom.:

AF XY:

0.00345

AC XY:

777

AN XY:

224996

show subpopulations

Gnomad4 AFR exome

AF:

0.0515

Gnomad4 AMR exome

AF:

0.00690

Gnomad4 ASJ exome

AF:

0.00813

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000216

Gnomad4 FIN exome

AF:

0.000306

Gnomad4 NFE exome

AF:

0.00174

Gnomad4 OTH exome

AF:

0.00934

GnomAD4 genome

AF:

0.0160

AC:

2432

AN:

152284

Hom.:

Cov.:

AF XY:

0.0152

AC XY:

1135

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0512

Gnomad4 AMR

AF:

0.00850

Gnomad4 ASJ

AF:

0.00691

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00163

Gnomad4 OTH

AF:

0.0142

Alfa

AF:

0.00226

Hom.:

Bravo

AF:

0.0183

Asia WGS

AF:

0.00722

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 25, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.9

DANN

Benign

0.37

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