Variant 22-36199341-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001386885.1(APOL4):c.71G>A(p.Gly24Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000425 in 1,614,126 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00043 ( 3 hom. )

Consequence

APOL4
NM_001386885.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.84

Variant links:

Genes affected

APOL4 (HGNC:14867): (apolipoprotein L4) This gene encodes a member of the apolipoprotein L family. The encoded protein 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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2020]

APOL4 links:

APOL4 (HGNC:):

APOL4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010401726).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOL4	NM_001386885.1 linkuse as main transcript	c.71G>A	p.Gly24Glu	missense_variant	2/4	ENST00000683024.1	NP_001373814.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOL4	ENST00000683024.1 linkuse as main transcript	c.71G>A	p.Gly24Glu	missense_variant	2/4		NM_001386885.1	ENSP00000507418.1		Q9BPW4-2

Frequencies

GnomAD3 genomes

AF:

0.000348

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000536

AC:

134

AN:

250126

Hom.:

AF XY:

0.000693

AC XY:

AN XY:

135578

show subpopulations

Gnomad AFR exome

AF:

0.0000641

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00137

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000680

Gnomad OTH exome

AF:

0.000988

GnomAD4 exome

AF:

0.000433

AC:

633

AN:

1461772

Hom.:

Cov.:

AF XY:

0.000483

AC XY:

351

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.000230

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00119

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000400

Gnomad4 OTH exome

AF:

0.000464

GnomAD4 genome

AF:

0.000348

AC:

AN:

152354

Hom.:

Cov.:

AF XY:

0.000389

AC XY:

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000456

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000486

Hom.:

Bravo

AF:

0.000325

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000229

AC:

ESP6500EA

AF:

0.000350

AC:

ExAC

AF:

0.000552

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000927

EpiControl

AF:

0.00113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 16, 2021

The c.80G>A (p.G27E) alteration is located in exon 3 (coding exon 2) of the APOL4 gene. This alteration results from a G to A substitution at nucleotide position 80, causing the glycine (G) at amino acid position 27 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.40

CADD

Benign

0.089

DANN

Benign

0.59

DEOGEN2

Benign

0.070

T;T

Eigen

Benign

-0.97

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0092

LIST_S2

Benign

0.32

.;T

M_CAP

Benign

0.0031

MetaRNN

Benign

0.010

T;T

MetaSVM

Benign

-0.75

PROVEAN

Pathogenic

-5.0

D;D

REVEL

Benign

0.041

Vest4

0.090

MVP

0.048

ClinPred

0.030

GERP RS

-2.4

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over