chr22-36143706-G-T

Variant names:

• chr22-36143706-G-T
• rs80575
• NM_145639.2:c.138-1648C>A

Variant summary

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

The NM_145639.2(APOL3):​c.138-1648C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 152,000 control chromosomes in the GnomAD database, including 24,701 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 (24701 hom., cov: 32)
• Consequence: APOL3 NM_145639.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.87
• Publications: 8 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOL3	NM_145639.2	c.138-1648C>A		intron_variant	Intron 3 of 3	ENST00000424878.4	NP_663614.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOL3	ENST00000424878.4	c.138-1648C>A		intron_variant	Intron 3 of 3	1	NM_145639.2	ENSP00000415779.3

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84924 AN: 151882 Hom.: 24697 Cov.: 32

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.733

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.582

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

GnomAD4 genome AF: 0.559 AC: 84962 AN: 152000 Hom.: 24701 Cov.: 32 AF XY: 0.558 AC XY: 41437 AN XY: 74282

African (AFR) AF: 0.411 AC: 17037 AN: 41424

American (AMR) AF: 0.504 AC: 7689 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.733 AC: 2544 AN: 3470

East Asian (EAS) AF: 0.348 AC: 1799 AN: 5164

South Asian (SAS) AF: 0.722 AC: 3481 AN: 4822

European-Finnish (FIN) AF: 0.615 AC: 6504 AN: 10568

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.646 AC: 43915 AN: 67972

Other (OTH) AF: 0.578 AC: 1218 AN: 2106

Alfa AF: 0.617 Hom.: 103843

Bravo AF: 0.536

Asia WGS AF: 0.555 AC: 1932 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.13
DANN	Benign	0.56
PhyloP100		-1.9
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: rs80575; hg19: chr22-36539754;