rs28360494

Variant names:

• chr22-36255185-T-G
• rs28360494
• NM_003661.4:c.44+186T>G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003661.4(APOL1):​c.44+186T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 152,164 control chromosomes in the GnomAD database, including 1,646 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.14 (1646 hom., cov: 33)
• Consequence: APOL1 NM_003661.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.591

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.07).
• BP6: Variant 22-36255185-T-G is Benign according to our data. Variant chr22-36255185-T-G is described in ClinVar as [Benign]. Clinvar id is 1289058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOL1	NM_003661.4	c.44+186T>G		intron_variant	Intron 2 of 5	ENST00000397278.8	NP_003652.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOL1	ENST00000397278.8	c.44+186T>G		intron_variant	Intron 2 of 5	1	NM_003661.4	ENSP00000380448.4

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21465 AN: 152046 Hom.: 1637 Cov.: 33

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.0554

Gnomad SAS AF: 0.0546

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.154

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.141 AC: 21510 AN: 152164 Hom.: 1646 Cov.: 33 AF XY: 0.142 AC XY: 10598 AN XY: 74392

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.156

Gnomad4 EAS AF: 0.0555

Gnomad4 SAS AF: 0.0538

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.153

Alfa AF: 0.139 Hom.: 237

Bravo AF: 0.141

Asia WGS AF: 0.0720 AC: 252 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.32
DANN	Benign	0.36

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: rs28360494; hg19: chr22-36651231;