rs5995251

Variant names:

• chr22-36204712-A-T
• rs5995251
• ENST00000352371.5:c.-104T>A

Variant summary

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

The ENST00000352371.5(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 ENST00000352371.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.601
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000352371.5. 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
	APOL4	NM_145660.2		c.-104T>A		5_prime_UTR	Exon 1 of 5	NP_663693.1
	APOL4	NM_030643.4		c.-302T>A		5_prime_UTR	Exon 1 of 6	NP_085146.2
	APOL4	NM_145661.2		c.-302T>A		5_prime_UTR	Exon 1 of 6	NP_663694.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOL4	ENST00000352371.5	TSL:1	c.-104T>A		5_prime_UTR	Exon 1 of 5	ENSP00000338260.3
	APOL4	ENST00000616056.4	TSL:1	c.-302T>A		5_prime_UTR	Exon 1 of 6	ENSP00000483497.1
	APOL4	ENST00000397275.6	TSL:1	c.-302T>A		5_prime_UTR	Exon 1 of 6	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

African (AFR) AF: 0.373 AC: 2460 AN: 6602

American (AMR) AF: 0.281 AC: 3811 AN: 13576

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 2062 AN: 7486

East Asian (EAS) AF: 0.0259 AC: 415 AN: 16016

South Asian (SAS) AF: 0.125 AC: 3005 AN: 24064

European-Finnish (FIN) AF: 0.333 AC: 6002 AN: 18012

Middle Eastern (MID) AF: 0.332 AC: 915 AN: 2756

European-Non Finnish (NFE) AF: 0.289 AC: 58186 AN: 201120

Other (OTH) AF: 0.282 AC: 4432 AN: 15740

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

African (AFR) AF: 0.399 AC: 16229 AN: 40630

American (AMR) AF: 0.334 AC: 5050 AN: 15116

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 1081 AN: 3432

East Asian (EAS) AF: 0.0342 AC: 177 AN: 5176

South Asian (SAS) AF: 0.150 AC: 719 AN: 4792

European-Finnish (FIN) AF: 0.383 AC: 3990 AN: 10430

Middle Eastern (MID) AF: 0.372 AC: 107 AN: 288

European-Non Finnish (NFE) AF: 0.333 AC: 22358 AN: 67100

Other (OTH) AF: 0.320 AC: 664 AN: 2074

Alfa AF: 0.364 Hom.: 1249

Asia WGS AF: 0.135 AC: 470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.8
DANN	Benign	0.58
PhyloP100		-0.60
PromoterAI		-0.028	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5995251; hg19: chr22-36600758;