rs2105915

Variant names:

• chr22-36156291-C-T
• rs2105915
• NM_145639.2:c.-88+4378G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145639.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOL3	NM_145639.2	MANE Select	c.-88+4378G>A		intron	N/A	NP_663614.1
	APOL3	NM_145640.2		c.223+4378G>A		intron	N/A	NP_663615.1
	APOL3	NM_001393587.1		c.-317+3086G>A		intron	N/A	NP_001380516.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOL3	ENST00000424878.4	TSL:1 MANE Select	c.-88+4378G>A		intron	N/A	ENSP00000415779.3
	APOL3	ENST00000349314.7	TSL:1	c.223+4378G>A		intron	N/A	ENSP00000344577.2
	APOL3	ENST00000361710.6	TSL:1	c.-378+4378G>A		intron	N/A	ENSP00000355164.2

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

African (AFR) AF: 0.107 AC: 4443 AN: 41472

American (AMR) AF: 0.235 AC: 3585 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 1282 AN: 3470

East Asian (EAS) AF: 0.107 AC: 553 AN: 5168

South Asian (SAS) AF: 0.329 AC: 1586 AN: 4816

European-Finnish (FIN) AF: 0.268 AC: 2832 AN: 10548

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.338 AC: 22984 AN: 67912

Other (OTH) AF: 0.278 AC: 586 AN: 2106

Alfa AF: 0.291 Hom.: 919

Bravo AF: 0.238

Asia WGS AF: 0.186 AC: 650 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	2.7
DANN	Benign	0.93
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2105915; hg19: chr22-36552339;