rs6000189

chr22-36204768-A-G

Variant summary

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

The ENST00000352371.5(APOL4):c.-160T>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 0.308 in 262,838 control chromosomes in the GnomAD database, including 13,938 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 (9965 hom., cov: 30)
  • Exomes 𝑓: 0.25 (3973 hom.)
• Consequence: APOL4 ENST00000352371.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOL4	NM_030643.4	c.-358T>C		5_prime_UTR_variant	1/6
APOL4	NM_145660.2	c.-160T>C		5_prime_UTR_variant	1/5
APOL4	NM_145661.2	c.-358T>C		5_prime_UTR_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOL4	ENST00000352371.5	c.-160T>C		5_prime_UTR_variant	1/5	1		A2
APOL4	ENST00000616056.4	c.-358T>C		5_prime_UTR_variant	1/6	1		P2
APOL4	ENST00000332987.5	c.-462T>C		5_prime_UTR_variant	1/5	2		P2

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53626 AN: 151608 Hom.: 9947 Cov.: 30

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.0338

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.341

GnomAD4 exome AF: 0.246 AC: 27312 AN: 111112 Hom.: 3973 Cov.: 3 AF XY: 0.239 AC XY: 14275 AN XY: 59652

Gnomad4 AFR exome AF: 0.363

Gnomad4 AMR exome AF: 0.247

Gnomad4 ASJ exome AF: 0.258

Gnomad4 EAS exome AF: 0.0239

Gnomad4 SAS exome AF: 0.114

Gnomad4 FIN exome AF: 0.309

Gnomad4 NFE exome AF: 0.271

Gnomad4 OTH exome AF: 0.276

GnomAD4 genome AF: 0.354 AC: 53694 AN: 151726 Hom.: 9965 Cov.: 30 AF XY: 0.352 AC XY: 26099 AN XY: 74114

Gnomad4 AFR AF: 0.421

Gnomad4 AMR AF: 0.350

Gnomad4 ASJ AF: 0.327

Gnomad4 EAS AF: 0.0340

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.392

Gnomad4 NFE AF: 0.350

Gnomad4 OTH AF: 0.337

Alfa AF: 0.361 Hom.: 2005

Bravo AF: 0.356

Asia WGS AF: 0.136 AC: 474 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	0.43
Dann	Benign	0.36

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: rs6000189; hg19: chr22-36600814;