22-36161718-C-T

Variant names:

• chr22-36161718-C-T
• rs132656
• ENST00000361710.6:c.-498-929G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000361710.6(APOL3):​c.-498-929G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 151,920 control chromosomes in the GnomAD database, including 22,401 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 0.53 (22401 hom., cov: 32)
• Consequence: APOL3 ENST00000361710.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOL3	NM_145641.3	c.-561-172G>A		intron_variant	Intron 1 of 4		NP_663616.1
APOL3	NM_145642.3	c.-498-929G>A		intron_variant	Intron 1 of 3		NP_663617.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOL3	ENST00000361710.6	c.-498-929G>A		intron_variant	Intron 1 of 3	1		ENSP00000355164.2
APOL3	ENST00000397287.6	c.-561-172G>A		intron_variant	Intron 1 of 4	1		ENSP00000380456.2

Frequencies

GnomAD3 genomes AF: 0.528 AC: 80138 AN: 151802 Hom.: 22380 Cov.: 32

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.666

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.542

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

GnomAD4 genome AF: 0.528 AC: 80185 AN: 151920 Hom.: 22401 Cov.: 32 AF XY: 0.538 AC XY: 39991 AN XY: 74268

African (AFR) AF: 0.373 AC: 15449 AN: 41384

American (AMR) AF: 0.659 AC: 10066 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.561 AC: 1945 AN: 3470

East Asian (EAS) AF: 0.851 AC: 4412 AN: 5182

South Asian (SAS) AF: 0.647 AC: 3115 AN: 4812

European-Finnish (FIN) AF: 0.666 AC: 7023 AN: 10550

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.536 AC: 36451 AN: 67948

Other (OTH) AF: 0.547 AC: 1149 AN: 2102

Alfa AF: 0.509 Hom.: 2963

Bravo AF: 0.520

Asia WGS AF: 0.752 AC: 2610 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.4
DANN	Benign	0.28
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs132656; hg19: chr22-36557766;