ENST00000352371.5:c.-187T>C

Variant names:

• chr22-36204795-A-G
• rs6000190
• ENST00000352371.5:c.-187T>C

Variant summary

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

The ENST00000352371.5(APOL4):​c.-187T>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 0.321 in 228,090 control chromosomes in the GnomAD database, including 12,821 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 (9974 hom., cov: 31)
  • Exomes 𝑓: 0.25 (2847 hom.)
• Consequence: APOL4 ENST00000352371.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.416 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.-187T>C		5_prime_UTR	Exon 1 of 5	NP_663693.1
	APOL4	NM_030643.4		c.-385T>C		5_prime_UTR	Exon 1 of 6	NP_085146.2
	APOL4	NM_145661.2		c.-385T>C		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.-187T>C		5_prime_UTR	Exon 1 of 5	ENSP00000338260.3
	APOL4	ENST00000616056.4	TSL:1	c.-385T>C		5_prime_UTR	Exon 1 of 6	ENSP00000483497.1
	APOL4	ENST00000449084.2	TSL:5	n.14T>C		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53664 AN: 151706 Hom.: 9956 Cov.: 31

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.0337

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: 0.254 AC: 19388 AN: 76266 Hom.: 2847 Cov.: 1 AF XY: 0.249 AC XY: 10049 AN XY: 40304

African (AFR) AF: 0.369 AC: 716 AN: 1938

American (AMR) AF: 0.291 AC: 824 AN: 2828

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 730 AN: 2754

East Asian (EAS) AF: 0.0279 AC: 150 AN: 5374

South Asian (SAS) AF: 0.124 AC: 729 AN: 5886

European-Finnish (FIN) AF: 0.315 AC: 1795 AN: 5696

Middle Eastern (MID) AF: 0.350 AC: 692 AN: 1976

European-Non Finnish (NFE) AF: 0.275 AC: 12312 AN: 44692

Other (OTH) AF: 0.281 AC: 1440 AN: 5122

GnomAD4 genome AF: 0.354 AC: 53732 AN: 151824 Hom.: 9974 Cov.: 31 AF XY: 0.352 AC XY: 26117 AN XY: 74184

African (AFR) AF: 0.421 AC: 17412 AN: 41356

American (AMR) AF: 0.350 AC: 5336 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 1137 AN: 3470

East Asian (EAS) AF: 0.0340 AC: 176 AN: 5176

South Asian (SAS) AF: 0.152 AC: 731 AN: 4802

European-Finnish (FIN) AF: 0.392 AC: 4127 AN: 10534

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.350 AC: 23758 AN: 67912

Other (OTH) AF: 0.338 AC: 711 AN: 2106

Alfa AF: 0.348 Hom.: 3902

Bravo AF: 0.356

Asia WGS AF: 0.135 AC: 473 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.5
DANN	Benign	0.41
PhyloP100		-1.9
PromoterAI		0.060	Neutral
Mutation Taster		=299/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6000190; hg19: chr22-36600841;