rs2017329

Variant names:

• chr22-36153118-T-A
• rs2017329
• NM_145639.2:c.-87-3976A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145639.2(APOL3):​c.-87-3976A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 150,360 control chromosomes in the GnomAD database, including 24,575 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 0.56 (24575 hom., cov: 31)
• Consequence: APOL3 NM_145639.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• Publications: 0 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOL3	NM_145639.2	c.-87-3976A>T		intron_variant	Intron 1 of 3	ENST00000424878.4	NP_663614.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOL3	ENST00000424878.4	c.-87-3976A>T		intron_variant	Intron 1 of 3	1	NM_145639.2	ENSP00000415779.3

Frequencies

GnomAD3 genomes AF: 0.564 AC: 84749 AN: 150248 Hom.: 24537 Cov.: 31

Gnomad AFR AF: 0.673

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.567

Gnomad OTH AF: 0.553

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.564 AC: 84829 AN: 150360 Hom.: 24575 Cov.: 31 AF XY: 0.555 AC XY: 40778 AN XY: 73424

African (AFR) AF: 0.674 AC: 27749 AN: 41182

American (AMR) AF: 0.431 AC: 6550 AN: 15184

Ashkenazi Jewish (ASJ) AF: 0.620 AC: 2142 AN: 3454

East Asian (EAS) AF: 0.150 AC: 775 AN: 5176

South Asian (SAS) AF: 0.496 AC: 2374 AN: 4782

European-Finnish (FIN) AF: 0.536 AC: 5465 AN: 10194

Middle Eastern (MID) AF: 0.579 AC: 169 AN: 292

European-Non Finnish (NFE) AF: 0.567 AC: 38037 AN: 67106

Other (OTH) AF: 0.549 AC: 1144 AN: 2084

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.552

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.20
DANN	Benign	0.32
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2017329; hg19: chr22-36549166;