chr22-36156354-T-C

Variant names:

• chr22-36156354-T-C
• rs132648
• NM_145639.2:c.-88+4315A>G

Variant summary

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

The NM_145639.2(APOL3):​c.-88+4315A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.892 in 152,216 control chromosomes in the GnomAD database, including 60,807 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 0.89 (60807 hom., cov: 32)
• Consequence: APOL3 NM_145639.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40
• Publications: 1 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 (EAS) allele frequency at 95% confidence interval = 0.969 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145639.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOL3	NM_145639.2	MANE Select	c.-88+4315A>G		intron	N/A	NP_663614.1
	APOL3	NM_145640.2		c.223+4315A>G		intron	N/A	NP_663615.1
	APOL3	NM_001393587.1		c.-317+3023A>G		intron	N/A	NP_001380516.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOL3	ENST00000424878.4	TSL:1 MANE Select	c.-88+4315A>G		intron	N/A	ENSP00000415779.3
	APOL3	ENST00000349314.7	TSL:1	c.223+4315A>G		intron	N/A	ENSP00000344577.2
	APOL3	ENST00000361710.6	TSL:1	c.-378+4315A>G		intron	N/A	ENSP00000355164.2

Frequencies

GnomAD3 genomes AF: 0.892 AC: 135616 AN: 152098 Hom.: 60746 Cov.: 32

Gnomad AFR AF: 0.970

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.913

Gnomad ASJ AF: 0.877

Gnomad EAS AF: 0.991

Gnomad SAS AF: 0.905

Gnomad FIN AF: 0.887

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.834

Gnomad OTH AF: 0.882

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

GnomAD4 genome AF: 0.892 AC: 135736 AN: 152216 Hom.: 60807 Cov.: 32 AF XY: 0.895 AC XY: 66589 AN XY: 74424

African (AFR) AF: 0.970 AC: 40315 AN: 41558

American (AMR) AF: 0.913 AC: 13953 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.877 AC: 3045 AN: 3472

East Asian (EAS) AF: 0.991 AC: 5119 AN: 5164

South Asian (SAS) AF: 0.905 AC: 4368 AN: 4824

European-Finnish (FIN) AF: 0.887 AC: 9414 AN: 10608

Middle Eastern (MID) AF: 0.901 AC: 265 AN: 294

European-Non Finnish (NFE) AF: 0.834 AC: 56709 AN: 67986

Other (OTH) AF: 0.884 AC: 1868 AN: 2114

Alfa AF: 0.876 Hom.: 8653

Bravo AF: 0.896

Asia WGS AF: 0.955 AC: 3321 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.9
DANN	Benign	0.17
PhyloP100		-1.4
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: rs132648; hg19: chr22-36552402;