22-36157133-A-G

Position:

• chr22-36157133-A-G

Variant summary

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

The NM_145639.2(APOL3):​c.-88+3536T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 412,220 control chromosomes in the GnomAD database, including 32,616 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 0.30 (9383 hom., cov: 32)
  • Exomes 𝑓: 0.40 (23233 hom.)
• Consequence: APOL3 NM_145639.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.123

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]

APOL3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOL3	NM_145639.2	c.-88+3536T>C		intron_variant		ENST00000424878.4	NP_663614.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOL3	ENST00000424878.4	c.-88+3536T>C		intron_variant		1	NM_145639.2	ENSP00000415779.3

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45697 AN: 151974 Hom.: 9369 Cov.: 32

Gnomad AFR AF: 0.0722

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.843

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.339

GnomAD4 exome AF: 0.396 AC: 102939 AN: 260128 Hom.: 23233 AF XY: 0.406 AC XY: 59824 AN XY: 147520

Gnomad4 AFR exome AF: 0.0656

Gnomad4 AMR exome AF: 0.634

Gnomad4 ASJ exome AF: 0.360

Gnomad4 EAS exome AF: 0.851

Gnomad4 SAS exome AF: 0.497

Gnomad4 FIN exome AF: 0.362

Gnomad4 NFE exome AF: 0.319

Gnomad4 OTH exome AF: 0.359

GnomAD4 genome AF: 0.301 AC: 45717 AN: 152092 Hom.: 9383 Cov.: 32 AF XY: 0.315 AC XY: 23450 AN XY: 74340

Gnomad4 AFR AF: 0.0721

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.356

Gnomad4 EAS AF: 0.843

Gnomad4 SAS AF: 0.518

Gnomad4 FIN AF: 0.389

Gnomad4 NFE AF: 0.320

Gnomad4 OTH AF: 0.345

Alfa AF: 0.335 Hom.: 6421

Bravo AF: 0.300

Asia WGS AF: 0.628 AC: 2177 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	6.4
DANN	Benign	0.89

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

Publications

LitVar

Other links and lift over

dbSNP: rs132649; hg19: chr22-36553181;