rs28391521

Variant names:

• chr22-36265015-A-G
• rs28391521
• NM_003661.4:c.315-136A>G

Your query was ambiguous. Multiple possible variants found:

• chr22-36265015-A-G
• chr22-36265015-A-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000397278.8(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 ENST00000397278.8 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.76
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• focal segmental glomerulosclerosis 4, susceptibility to

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000397278.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOL1	NM_003661.4	MANE Select	c.315-136A>G		intron	N/A	NP_003652.2
	APOL1	NM_145343.3		c.363-136A>G		intron	N/A	NP_663318.1
	APOL1	NM_001136540.2		c.315-136A>G		intron	N/A	NP_001130012.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOL1	ENST00000397278.8	TSL:1 MANE Select	c.315-136A>G		intron	N/A	ENSP00000380448.4
	APOL1	ENST00000319136.8	TSL:1	c.363-136A>G		intron	N/A	ENSP00000317674.4
	APOL1	ENST00000438034.6	TSL:4	c.402-136A>G		intron	N/A	ENSP00000404525.2

Frequencies

GnomAD3 genomes AF: 0.857 AC: 130163 AN: 151826 Hom.: 56138 Cov.: 28

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

African (AFR) AF: 0.957 AC: 21127 AN: 22086

American (AMR) AF: 0.893 AC: 19434 AN: 21758

Ashkenazi Jewish (ASJ) AF: 0.832 AC: 14294 AN: 17176

East Asian (EAS) AF: 0.843 AC: 28462 AN: 33754

South Asian (SAS) AF: 0.834 AC: 48731 AN: 58398

European-Finnish (FIN) AF: 0.843 AC: 38521 AN: 45670

Middle Eastern (MID) AF: 0.772 AC: 2336 AN: 3024

European-Non Finnish (NFE) AF: 0.808 AC: 599829 AN: 741990

Other (OTH) AF: 0.825 AC: 35647 AN: 43188

GnomAD4 genome AF: 0.857 AC: 130275 AN: 151944 Hom.: 56192 Cov.: 28 AF XY: 0.860 AC XY: 63897 AN XY: 74272

African (AFR) AF: 0.952 AC: 39456 AN: 41448

American (AMR) AF: 0.873 AC: 13342 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.819 AC: 2844 AN: 3472

East Asian (EAS) AF: 0.844 AC: 4345 AN: 5150

South Asian (SAS) AF: 0.842 AC: 4040 AN: 4800

European-Finnish (FIN) AF: 0.844 AC: 8910 AN: 10562

Middle Eastern (MID) AF: 0.823 AC: 242 AN: 294

European-Non Finnish (NFE) AF: 0.804 AC: 54607 AN: 67922

Other (OTH) AF: 0.836 AC: 1763 AN: 2108

Alfa AF: 0.902 Hom.: 12771

Bravo AF: 0.865

Asia WGS AF: 0.852 AC: 2961 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.59
PhyloP100		-2.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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