22-36155110-T-C

Variant names:

• chr22-36155110-T-C
• rs132647
• NM_145639.2:c.-88+5559A>G

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+5559A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 152,110 control chromosomes in the GnomAD database, including 7,716 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 0.27 (7716 hom., cov: 32)
• Consequence: APOL3 NM_145639.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.531
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.821 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOL3	NM_145639.2	MANE Select	c.-88+5559A>G		intron	N/A	NP_663614.1
	APOL3	NM_145640.2		c.223+5559A>G		intron	N/A	NP_663615.1
	APOL3	NM_001393587.1		c.-317+4267A>G		intron	N/A	NP_001380516.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOL3	ENST00000424878.4	TSL:1 MANE Select	c.-88+5559A>G		intron	N/A	ENSP00000415779.3
	APOL3	ENST00000349314.7	TSL:1	c.223+5559A>G		intron	N/A	ENSP00000344577.2
	APOL3	ENST00000361710.6	TSL:1	c.-378+5559A>G		intron	N/A	ENSP00000355164.2

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41549 AN: 151992 Hom.: 7700 Cov.: 32

Gnomad AFR AF: 0.0959

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.842

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.302

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

GnomAD4 genome AF: 0.273 AC: 41579 AN: 152110 Hom.: 7716 Cov.: 32 AF XY: 0.286 AC XY: 21278 AN XY: 74348

African (AFR) AF: 0.0958 AC: 3977 AN: 41516

American (AMR) AF: 0.471 AC: 7207 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 992 AN: 3472

East Asian (EAS) AF: 0.842 AC: 4342 AN: 5156

South Asian (SAS) AF: 0.440 AC: 2113 AN: 4806

European-Finnish (FIN) AF: 0.342 AC: 3618 AN: 10588

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.270 AC: 18321 AN: 67962

Other (OTH) AF: 0.308 AC: 650 AN: 2112

Alfa AF: 0.275 Hom.: 20253

Bravo AF: 0.280

Asia WGS AF: 0.606 AC: 2100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.2
DANN	Benign	0.79
PhyloP100		-0.53
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: rs132647; hg19: chr22-36551158;