22-36257229-G-A

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.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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.222

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=-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_single_submitter, 1 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/exons	MANE	UniProt
APOL1	NM_003661.4	c.99-90G>A		intron_variant		ENST00000397278.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOL1	ENST00000397278.8	c.99-90G>A		intron_variant		1	NM_003661.4	A2

Frequencies

GnomAD3 genomes AF: 0.0922 AC: 14019 AN: 152118 Hom.: 718 Cov.: 32

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.: 28 AF XY: 0.100 AC XY: 72454 AN XY: 722024

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.: 32 AF XY: 0.0934 AC XY: 6954 AN XY: 74446

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: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	-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

Other links and lift over

dbSNP: rs4820224; hg19: chr22-36653275; COSMIC: COSV59869216;