chr22-36161452-C-T

Position:

• chr22-36161452-C-T

Variant summary

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

The NM_145641.3(APOL3):​c.-499+32G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 165,378 control chromosomes in the GnomAD database, including 12,998 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 0.34 (11512 hom., cov: 32)
  • Exomes 𝑓: 0.45 (1486 hom.)
• Consequence: APOL3 NM_145641.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.835

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOL3	NM_145641.3	c.-499+32G>A		intron_variant			NP_663616.1
APOL3	NM_145642.3	c.-498-663G>A		intron_variant			NP_663617.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOL3	ENST00000361710.6	c.-498-663G>A		intron_variant		1		ENSP00000355164.2
APOL3	ENST00000397287.6	c.-499+32G>A		intron_variant		1		ENSP00000380456.2

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52286 AN: 152016 Hom.: 11493 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.833

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.391

GnomAD4 exome AF: 0.449 AC: 5946 AN: 13244 Hom.: 1486 Cov.: 0 AF XY: 0.450 AC XY: 3121 AN XY: 6932

Gnomad4 AFR exome AF: 0.0762

Gnomad4 AMR exome AF: 0.597

Gnomad4 ASJ exome AF: 0.439

Gnomad4 EAS exome AF: 0.839

Gnomad4 SAS exome AF: 0.507

Gnomad4 FIN exome AF: 0.381

Gnomad4 NFE exome AF: 0.369

Gnomad4 OTH exome AF: 0.420

GnomAD4 genome AF: 0.344 AC: 52315 AN: 152134 Hom.: 11512 Cov.: 32 AF XY: 0.357 AC XY: 26572 AN XY: 74372

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.550

Gnomad4 ASJ AF: 0.422

Gnomad4 EAS AF: 0.833

Gnomad4 SAS AF: 0.541

Gnomad4 FIN AF: 0.433

Gnomad4 NFE AF: 0.370

Gnomad4 OTH AF: 0.397

Alfa AF: 0.211 Hom.: 525

Bravo AF: 0.342

Asia WGS AF: 0.661 AC: 2294 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.042
DANN	Benign	0.28

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs132654; hg19: chr22-36557500;