rs2105915

chr22-36156291-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145639.2(APOL3):c.-88+4378G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 151,954 control chromosomes in the GnomAD database, including 5,586 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.25 (5586 hom., cov: 31)
• Consequence: APOL3 NM_145639.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

Genes affected

APOL3 (HGNC:14868): (apolipoprotein L3) This gene is a member of the apolipoprotein L gene family, and it is present in a cluster with other family members on chromosome 22. The encoded protein is found in the cytoplasm, where it may affect the movement of lipids, including cholesterol, and/or allow the binding of lipids to organelles. In addition, expression of this gene is up-regulated by tumor necrosis factor-alpha in endothelial cells lining the normal and atherosclerotic iliac artery and aorta. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOL3	NM_145639.2	c.-88+4378G>A		intron_variant		ENST00000424878.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOL3	ENST00000424878.4	c.-88+4378G>A		intron_variant		1	NM_145639.2	A2

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38222 AN: 151836 Hom.: 5590 Cov.: 31

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.281

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

GnomAD4 genome AF: 0.252 AC: 38229 AN: 151954 Hom.: 5586 Cov.: 31 AF XY: 0.250 AC XY: 18551 AN XY: 74262

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.235

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.107

Gnomad4 SAS AF: 0.329

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.338

Gnomad4 OTH AF: 0.278

Alfa AF: 0.298 Hom.: 914

Bravo AF: 0.238

Asia WGS AF: 0.186 AC: 650 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
Cadd	Benign	2.7
Dann	Benign	0.93

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: rs2105915; hg19: chr22-36552339;