Genetic Variant APOL1:c.-19-171G>T (chr22-36254766-G-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_003661.4(APOL1):c.-19-171G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00862 in 723,788 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0063 ( 9 hom., cov: 32)

Exomes 𝑓: 0.0092 ( 40 hom. )

Consequence

APOL1
NM_003661.4 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.73

Variant links:

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]

APOL1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 22-36254766-G-T is Benign according to our data. Variant chr22-36254766-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1706719.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00634 (964/152160) while in subpopulation SAS AF= 0.0189 (91/4818). AF 95% confidence interval is 0.0158. There are 9 homozygotes in gnomad4. There are 475 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOL1	NM_003661.4 link	c.-19-171G>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 link	c.-19-171G>T		intron_variant	Intron 1 of 5	1	NM_003661.4	ENSP00000380448.4		O14791-1

Frequencies

GnomAD3 genomes

AF:

0.00635

AC:

966

AN:

152042

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00147

Gnomad AMI

AF:

0.00220

Gnomad AMR

AF:

0.00589

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0191

Gnomad FIN

AF:

0.00775

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00888

Gnomad OTH

AF:

0.00527

GnomAD4 exome

AF:

0.00923

AC:

5276

AN:

571628

Hom.:

AF XY:

0.00985

AC XY:

2941

AN XY:

298644

show subpopulations

Gnomad4 AFR exome

AF:

0.00116

Gnomad4 AMR exome

AF:

0.00387

Gnomad4 ASJ exome

AF:

0.00703

Gnomad4 EAS exome

AF:

0.0000411

Gnomad4 SAS exome

AF:

0.0195

Gnomad4 FIN exome

AF:

0.00859

Gnomad4 NFE exome

AF:

0.00928

Gnomad4 OTH exome

AF:

0.00755

GnomAD4 genome

AF:

0.00634

AC:

964

AN:

152160

Hom.:

Cov.:

AF XY:

0.00639

AC XY:

475

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.00147

Gnomad4 AMR

AF:

0.00589

Gnomad4 ASJ

AF:

0.00634

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0189

Gnomad4 FIN

AF:

0.00775

Gnomad4 NFE

AF:

0.00887

Gnomad4 OTH

AF:

0.00522

Alfa

AF:

0.00889

Hom.:

Bravo

AF:

0.00546

Asia WGS

AF:

0.00664

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 10, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.085

DANN

Benign

0.60

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