22-36166188-G-T

Position:

• chr22-36166188-G-T

Variant summary

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

The 22-36166188-G-T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 151,986 control chromosomes in the GnomAD database, including 28,326 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 0.61 (28326 hom., cov: 31)
  • Exomes 𝑓: 0.75 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: APOL3 ENST00000361710.6 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.137

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOL3	NM_145641.3			upstream_gene_variant			NP_663616.1
APOL3	NM_145642.3			upstream_gene_variant			NP_663617.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOL3	ENST00000361710.6			upstream_gene_variant		1		ENSP00000355164
APOL3	ENST00000397287.6			upstream_gene_variant		1		ENSP00000380456

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91856 AN: 151868 Hom.: 28279 Cov.: 31

Gnomad AFR AF: 0.601

Gnomad AMI AF: 0.450

Gnomad AMR AF: 0.692

Gnomad ASJ AF: 0.583

Gnomad EAS AF: 0.863

Gnomad SAS AF: 0.662

Gnomad FIN AF: 0.684

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.612

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.750 AC: 3 AN: 4 Hom.: 1 Cov.: 0 AF XY: 0.750 AC XY: 3 AN XY: 4

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.605 AC: 91960 AN: 151986 Hom.: 28326 Cov.: 31 AF XY: 0.613 AC XY: 45546 AN XY: 74282

Gnomad4 AFR AF: 0.601

Gnomad4 AMR AF: 0.692

Gnomad4 ASJ AF: 0.583

Gnomad4 EAS AF: 0.863

Gnomad4 SAS AF: 0.662

Gnomad4 FIN AF: 0.684

Gnomad4 NFE AF: 0.555

Gnomad4 OTH AF: 0.616

Alfa AF: 0.582 Hom.: 7208

Bravo AF: 0.605

Asia WGS AF: 0.786 AC: 2729 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.5
DANN	Benign	0.29

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs132660; hg19: chr22-36562236;