Genetic Variant APOL1:c.99-90G>A (chr22-36257229-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_003661.4(APOL1):c.99-90G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,603,610 control chromosomes in the GnomAD database, including 8,780 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.092 ( 716 hom., cov: 32)

Exomes 𝑓: 0.10 ( 8064 hom. )

Consequence

APOL1
NM_003661.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.222

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=-0.91).

BP6

Variant 22-36257229-G-A is Benign according to our data. Variant chr22-36257229-G-A is described in ClinVar as [Benign]. Clinvar id is 1290732.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOL1	NM_003661.4 link	c.99-90G>A		intron_variant	Intron 3 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.99-90G>A		intron_variant	Intron 3 of 5	1	NM_003661.4	ENSP00000380448.4		O14791-1

Frequencies

GnomAD3 genomes

AF:

0.0922

AC:

14019

AN:

152118

Hom.:

718

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0566

Gnomad AMI

AF:

0.137

Gnomad AMR

AF:

0.0903

Gnomad ASJ

AF:

0.138

Gnomad EAS

AF:

0.0412

Gnomad SAS

AF:

0.0528

Gnomad FIN

AF:

0.141

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.110

Gnomad OTH

AF:

0.116

GnomAD4 exome

AF:

0.101

AC:

147245

AN:

1451374

Hom.:

8064

Cov.:

AF XY:

0.100

AC XY:

72454

AN XY:

722024

show subpopulations

Gnomad4 AFR exome

AF:

0.0543

Gnomad4 AMR exome

AF:

0.0691

Gnomad4 ASJ exome

AF:

0.143

Gnomad4 EAS exome

AF:

0.0371

Gnomad4 SAS exome

AF:

0.0504

Gnomad4 FIN exome

AF:

0.137

Gnomad4 NFE exome

AF:

0.108

Gnomad4 OTH exome

AF:

0.0993

GnomAD4 genome

AF:

0.0922

AC:

14029

AN:

152236

Hom.:

716

Cov.:

AF XY:

0.0934

AC XY:

6954

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0568

Gnomad4 AMR

AF:

0.0903

Gnomad4 ASJ

AF:

0.138

Gnomad4 EAS

AF:

0.0412

Gnomad4 SAS

AF:

0.0523

Gnomad4 FIN

AF:

0.141

Gnomad4 NFE

AF:

0.110

Gnomad4 OTH

AF:

0.115

Alfa

AF:

0.109

Hom.:

1424

Bravo

AF:

0.0907

Asia WGS

AF:

0.0480

AC:

166

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

- -

Nov 10, 2018

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

-0.91

CADD

Benign

1.1

DANN

Benign

0.24

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