22-36161452-C-G

Variant names:

• chr22-36161452-C-G
• rs132654
• ENST00000361710.6:c.-498-663G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000361710.6(APOL3):​c.-498-663G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: APOL3 ENST00000361710.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.835
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000361710.6. 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_145641.3		c.-499+32G>C		intron	N/A	NP_663616.1
	APOL3	NM_145642.3		c.-498-663G>C		intron	N/A	NP_663617.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOL3	ENST00000361710.6	TSL:1	c.-498-663G>C		intron	N/A	ENSP00000355164.2
	APOL3	ENST00000397287.6	TSL:1	c.-499+32G>C		intron	N/A	ENSP00000380456.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 13288 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 6956

African (AFR) AF: 0.00 AC: 0 AN: 210

American (AMR) AF: 0.00 AC: 0 AN: 2358

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 164

East Asian (EAS) AF: 0.00 AC: 0 AN: 656

South Asian (SAS) AF: 0.00 AC: 0 AN: 1712

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 272

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 14

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 7310

Other (OTH) AF: 0.00 AC: 0 AN: 592

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0080
DANN	Benign	0.18
PhyloP100		-0.83

Splicing

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

Other links and lift over

dbSNP: rs132654; hg19: chr22-36557500;