rs28391521

Positions:

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

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.76

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]

ACMG classification

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	Protein	UniProt
APOL1	NM_003661.4	c.315-136A>G		intron_variant		ENST00000397278.8	NP_003652.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOL1	ENST00000397278.8	c.315-136A>G		intron_variant		1	NM_003661.4	ENSP00000380448.4

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

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

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

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 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

Other links and lift over

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