rs5995251

Positions:

• chr22-36204712-A-T

Variant summary

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

The NM_145660.2(APOL4):​c.-104T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 455,320 control chromosomes in the GnomAD database, including 19,746 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 0.34 (7779 hom., cov: 30)
  • Exomes 𝑓: 0.27 (11967 hom.)
• Consequence: APOL4 NM_145660.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.601

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]

APOL4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOL4	NM_145660.2	c.-104T>A		5_prime_UTR_variant	1/5		NP_663693.1
APOL4	NM_030643.4	c.-302T>A		5_prime_UTR_variant	1/6		NP_085146.2
APOL4	NM_145661.2	c.-302T>A		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.-104T>A		5_prime_UTR_variant	1/5	1		ENSP00000338260.3
APOL4	ENST00000616056.4	c.-302T>A		5_prime_UTR_variant	1/6	1		ENSP00000483497.1
APOL4	ENST00000397275.6	c.-302T>A		5_prime_UTR_variant	1/6	1		ENSP00000380445.2

Frequencies

GnomAD3 genomes AF: 0.337 AC: 50524 AN: 149826 Hom.: 7759 Cov.: 30

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.0339

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.376

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.324

GnomAD4 exome AF: 0.266 AC: 81288 AN: 305372 Hom.: 11967 Cov.: 5 AF XY: 0.261 AC XY: 42624 AN XY: 163206

Gnomad4 AFR exome AF: 0.373

Gnomad4 AMR exome AF: 0.281

Gnomad4 ASJ exome AF: 0.275

Gnomad4 EAS exome AF: 0.0259

Gnomad4 SAS exome AF: 0.125

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.289

Gnomad4 OTH exome AF: 0.282

GnomAD4 genome AF: 0.337 AC: 50596 AN: 149948 Hom.: 7779 Cov.: 30 AF XY: 0.337 AC XY: 24701 AN XY: 73352

Gnomad4 AFR AF: 0.399

Gnomad4 AMR AF: 0.334

Gnomad4 ASJ AF: 0.315

Gnomad4 EAS AF: 0.0342

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.383

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.320

Alfa AF: 0.364 Hom.: 1249

Asia WGS AF: 0.135 AC: 470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.8
DANN	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs5995251; hg19: chr22-36600758;