chr22-36253958-C-T

Variant names:

• chr22-36253958-C-T
• rs139494181
• ENST00000319136:c.-5C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_145343.3(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 NM_145343.3 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• 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

Our verdict: Benign. The variant received -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 GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOL1	NM_003661.4	c.-20+739C>T		intron_variant	Intron 1 of 5	ENST00000397278.8	NP_003652.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOL1	ENST00000397278.8	c.-20+739C>T		intron_variant	Intron 1 of 5	1	NM_003661.4	ENSP00000380448.4

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

GnomAD2 exomes AF: 0.00907 AC: 2280 AN: 251444 AF XY: 0.00914

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 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 AC: 54 AN: 33480

Gnomad4 AMR exome AF: 0.00957 AC: 428 AN: 44724

Gnomad4 ASJ exome AF: 0.0224 AC: 585 AN: 26130

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39700

Gnomad4 SAS exome AF: 0.00319 AC: 275 AN: 86256

Gnomad4 FIN exome AF: 0.0132 AC: 706 AN: 53390

Gnomad4 NFE exome AF: 0.00901 AC: 10016 AN: 1111934

Gnomad4 Remaining exome AF: 0.00952 AC: 575 AN: 60392

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 AC: 0.00142045 AN: 0.00142045

Gnomad4 AMR AF: 0.0122 AC: 0.0122206 AN: 0.0122206

Gnomad4 ASJ AF: 0.0271 AC: 0.0270737 AN: 0.0270737

Gnomad4 EAS AF: 0.000386 AC: 0.000385505 AN: 0.000385505

Gnomad4 SAS AF: 0.00290 AC: 0.00289975 AN: 0.00289975

Gnomad4 FIN AF: 0.0182 AC: 0.018211 AN: 0.018211

Gnomad4 NFE AF: 0.0100 AC: 0.0100253 AN: 0.0100253

Gnomad4 OTH AF: 0.00898 AC: 0.00897921 AN: 0.00897921

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:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

APOL1: BP4, BS1, BS2 -

Aug 20, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

APOL1-related disorder Benign:1

Sep 26, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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
Mutation Taster		=100/0	polymorphism

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;