rs28391521

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_003661.4(APOL1):​c.315-136A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.824 in 1,138,988 control chromosomes in the GnomAD database, including 388,049 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.86 ( 56192 hom., cov: 28)
Exomes 𝑓: 0.82 ( 331857 hom. )

Consequence

APOL1
NM_003661.4 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.76
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-1.03).
BP6
Variant 22-36265015-A-G is Benign according to our data. Variant chr22-36265015-A-G is described in ClinVar as [Benign]. Clinvar id is 1183411.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.944 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
APOL1NM_003661.4 linkuse as main transcriptc.315-136A>G intron_variant ENST00000397278.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
APOL1ENST00000397278.8 linkuse as main transcriptc.315-136A>G intron_variant 1 NM_003661.4 A2O14791-1

Frequencies

GnomAD3 genomes
AF:
0.857
AC:
130163
AN:
151826
Hom.:
56138
Cov.:
28
show subpopulations
Gnomad AFR
AF:
0.952
Gnomad AMI
AF:
0.796
Gnomad AMR
AF:
0.873
Gnomad ASJ
AF:
0.819
Gnomad EAS
AF:
0.844
Gnomad SAS
AF:
0.842
Gnomad FIN
AF:
0.844
Gnomad MID
AF:
0.823
Gnomad NFE
AF:
0.804
Gnomad OTH
AF:
0.835
GnomAD4 exome
AF:
0.819
AC:
808381
AN:
987044
Hom.:
331857
AF XY:
0.819
AC XY:
404829
AN XY:
494586
show subpopulations
Gnomad4 AFR exome
AF:
0.957
Gnomad4 AMR exome
AF:
0.893
Gnomad4 ASJ exome
AF:
0.832
Gnomad4 EAS exome
AF:
0.843
Gnomad4 SAS exome
AF:
0.834
Gnomad4 FIN exome
AF:
0.843
Gnomad4 NFE exome
AF:
0.808
Gnomad4 OTH exome
AF:
0.825
GnomAD4 genome
AF:
0.857
AC:
130275
AN:
151944
Hom.:
56192
Cov.:
28
AF XY:
0.860
AC XY:
63897
AN XY:
74272
show subpopulations
Gnomad4 AFR
AF:
0.952
Gnomad4 AMR
AF:
0.873
Gnomad4 ASJ
AF:
0.819
Gnomad4 EAS
AF:
0.844
Gnomad4 SAS
AF:
0.842
Gnomad4 FIN
AF:
0.844
Gnomad4 NFE
AF:
0.804
Gnomad4 OTH
AF:
0.836
Alfa
AF:
0.828
Hom.:
6125
Bravo
AF:
0.865
Asia WGS
AF:
0.852
AC:
2961
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 submitterclinical testingGeneDxNov 10, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
CADD
Benign
1.1
DANN
Benign
0.59

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.

Other links and lift over

dbSNP: rs28391521; hg19: chr22-36661061; COSMIC: COSV59868406; COSMIC: COSV59868406; API