rs2097465

Positions:

• chr22-36155868-C-T

Variant summary

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

The NM_145639.2(APOL3):​c.-88+4801G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 159,682 control chromosomes in the GnomAD database, including 5,912 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 0.25 (5612 hom., cov: 32)
  • Exomes 𝑓: 0.29 (300 hom.)
• Consequence: APOL3 NM_145639.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.359

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=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOL3	NM_145639.2	c.-88+4801G>A		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+4801G>A		intron_variant		1	NM_145639.2	ENSP00000415779	A2

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38341 AN: 152036 Hom.: 5616 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.309

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.282

GnomAD4 exome AF: 0.289 AC: 2178 AN: 7528 Hom.: 300 Cov.: 0 AF XY: 0.295 AC XY: 1173 AN XY: 3980

Gnomad4 AFR exome AF: 0.196

Gnomad4 AMR exome AF: 0.236

Gnomad4 ASJ exome AF: 0.400

Gnomad4 EAS exome AF: 0.108

Gnomad4 SAS exome AF: 0.336

Gnomad4 FIN exome AF: 0.277

Gnomad4 NFE exome AF: 0.333

Gnomad4 OTH exome AF: 0.280

GnomAD4 genome AF: 0.252 AC: 38348 AN: 152154 Hom.: 5612 Cov.: 32 AF XY: 0.250 AC XY: 18618 AN XY: 74374

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.235

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.107

Gnomad4 SAS AF: 0.329

Gnomad4 FIN AF: 0.269

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.279

Alfa AF: 0.327 Hom.: 11169

Bravo AF: 0.238

Asia WGS AF: 0.186 AC: 651 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.3
DANN	Benign	0.63

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: rs2097465; hg19: chr22-36551916;