rs5995250

Positions:

• chr22-36204690-A-G

Variant summary

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

The ENST00000352371.5(APOL4):​c.-82T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 572,802 control chromosomes in the GnomAD database, including 27,164 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 0.35 (7505 hom., cov: 30)
  • Exomes 𝑓: 0.29 (19659 hom.)
• Consequence: APOL4 ENST00000352371.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0170

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOL4	NM_030643.4	c.-280T>C		5_prime_UTR_variant	1/6		NP_085146.2
APOL4	NM_145660.2	c.-82T>C		5_prime_UTR_variant	1/5		NP_663693.1
APOL4	NM_145661.2	c.-280T>C		5_prime_UTR_variant	1/6		NP_663694.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOL4	ENST00000352371.5	c.-82T>C		5_prime_UTR_variant	1/5	1		ENSP00000338260	A2
APOL4	ENST00000397275.6	c.-280T>C		5_prime_UTR_variant	1/6	1		ENSP00000380445
APOL4	ENST00000616056.4	c.-280T>C		5_prime_UTR_variant	1/6	1		ENSP00000483497	P2

Frequencies

GnomAD3 genomes AF: 0.351 AC: 50234 AN: 142996 Hom.: 7486 Cov.: 30

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.0384

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.343

GnomAD4 exome AF: 0.292 AC: 125466 AN: 429674 Hom.: 19659 Cov.: 6 AF XY: 0.285 AC XY: 64407 AN XY: 225856

Gnomad4 AFR exome AF: 0.389

Gnomad4 AMR exome AF: 0.284

Gnomad4 ASJ exome AF: 0.288

Gnomad4 EAS exome AF: 0.0274

Gnomad4 SAS exome AF: 0.132

Gnomad4 FIN exome AF: 0.344

Gnomad4 NFE exome AF: 0.316

Gnomad4 OTH exome AF: 0.297

GnomAD4 genome AF: 0.351 AC: 50304 AN: 143128 Hom.: 7505 Cov.: 30 AF XY: 0.350 AC XY: 24559 AN XY: 70150

Gnomad4 AFR AF: 0.414

Gnomad4 AMR AF: 0.345

Gnomad4 ASJ AF: 0.327

Gnomad4 EAS AF: 0.0387

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.391

Gnomad4 NFE AF: 0.346

Gnomad4 OTH AF: 0.339

Alfa AF: 0.359 Hom.: 1979

Bravo AF: 0.356

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.7
DANN	Benign	0.43

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: rs5995250; hg19: chr22-36600736;