rs5845253

chr22-36191797-ACT-Achr22-36191797-ACT-ACTCT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001386885.1(APOL4):c.323_324del(p.Glu108ValfsTer21) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 1,613,480 control chromosomes in the GnomAD database, including 190,083 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.40 (13527 hom., cov: 0)
  • Exomes 𝑓: 0.49 (176556 hom.)
• Consequence: APOL4 NM_001386885.1 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.263

Genes affected

APOL4 (HGNC:14867): (apolipoprotein L4) This gene encodes a member of the apolipoprotein L family. The encoded protein may play a role in lipid exchange and transport throughout the body, as well as in reverse cholesterol transport from peripheral cells to the liver. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2020]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOL4	NM_001386885.1	c.323_324del	p.Glu108ValfsTer21	frameshift_variant	4/4	ENST00000683024.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOL4	ENST00000683024.1	c.323_324del	p.Glu108ValfsTer21	frameshift_variant	4/4		NM_001386885.1	P2

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61239 AN: 151702 Hom.: 13508 Cov.: 0

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.369

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.433

GnomAD4 exome AF: 0.485 AC: 709449 AN: 1461658 Hom.: 176556 AF XY: 0.485 AC XY: 352983 AN XY: 727112

Gnomad4 AFR exome AF: 0.224

Gnomad4 AMR exome AF: 0.444

Gnomad4 ASJ exome AF: 0.508

Gnomad4 EAS exome AF: 0.184

Gnomad4 SAS exome AF: 0.449

Gnomad4 FIN exome AF: 0.448

Gnomad4 NFE exome AF: 0.510

Gnomad4 OTH exome AF: 0.470

GnomAD4 genome AF: 0.404 AC: 61298 AN: 151822 Hom.: 13527 Cov.: 0 AF XY: 0.400 AC XY: 29667 AN XY: 74198

Gnomad4 AFR AF: 0.233

Gnomad4 AMR AF: 0.418

Gnomad4 ASJ AF: 0.513

Gnomad4 EAS AF: 0.182

Gnomad4 SAS AF: 0.427

Gnomad4 FIN AF: 0.443

Gnomad4 NFE AF: 0.507

Gnomad4 OTH AF: 0.435

Alfa AF: 0.224 Hom.: 1777

Bravo AF: 0.395

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs5845253; hg19: chr22-36587845;