22-36253958-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The ENST00000319136.8(APOL1):c.-5C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00865 in 1,614,048 control chromosomes in the GnomAD database, including 80 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0082 (8 hom., cov: 32)
  • Exomes 𝑓: 0.0087 (72 hom.)
• Consequence: APOL1 ENST00000319136.8 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.497

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 22-36253958-C-T is Benign according to our data. Variant chr22-36253958-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1316241.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOL1	NM_003661.4	c.-20+739C>T		intron_variant		ENST00000397278.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOL1	ENST00000397278.8	c.-20+739C>T		intron_variant		1	NM_003661.4	A2

Frequencies

GnomAD3 genomes AF: 0.00824 AC: 1254 AN: 152156 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.00142

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0122

Gnomad ASJ AF: 0.0271

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.0182

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0100

Gnomad OTH AF: 0.00907

GnomAD3 exomes AF: 0.00907 AC: 2280 AN: 251444 Hom.: 23 AF XY: 0.00914 AC XY: 1242 AN XY: 135890

Gnomad AFR exome AF: 0.00166

Gnomad AMR exome AF: 0.00986

Gnomad ASJ exome AF: 0.0219

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00291

Gnomad FIN exome AF: 0.0152

Gnomad NFE exome AF: 0.0106

Gnomad OTH exome AF: 0.0104

GnomAD4 exome AF: 0.00870 AC: 12712 AN: 1461774 Hom.: 72 Cov.: 30 AF XY: 0.00868 AC XY: 6313 AN XY: 727180

Gnomad4 AFR exome AF: 0.00161

Gnomad4 AMR exome AF: 0.00957

Gnomad4 ASJ exome AF: 0.0224

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00319

Gnomad4 FIN exome AF: 0.0132

Gnomad4 NFE exome AF: 0.00901

Gnomad4 OTH exome AF: 0.00952

GnomAD4 genome AF: 0.00824 AC: 1254 AN: 152274 Hom.: 8 Cov.: 32 AF XY: 0.00853 AC XY: 635 AN XY: 74446

Gnomad4 AFR AF: 0.00142

Gnomad4 AMR AF: 0.0122

Gnomad4 ASJ AF: 0.0271

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00290

Gnomad4 FIN AF: 0.0182

Gnomad4 NFE AF: 0.0100

Gnomad4 OTH AF: 0.00898

Alfa AF: 0.00954 Hom.: 4

Bravo AF: 0.00760

EpiCase AF: 0.0156

EpiControl AF: 0.0124

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 20, 2019	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2023	APOL1: BP4, BS1, BS2 -

APOL1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 26, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.53
Dann	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs139494181; hg19: chr22-36650004;