chr22-36204768-A-G

Variant names:

• chr22-36204768-A-G
• rs6000189
• ENST00000352371.5:c.-160T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.92).
• 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.-160T>C		5_prime_UTR	Exon 1 of 5	NP_663693.1
	APOL4	NM_030643.4		c.-358T>C		5_prime_UTR	Exon 1 of 6	NP_085146.2
	APOL4	NM_145661.2		c.-358T>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.-160T>C		5_prime_UTR	Exon 1 of 5	ENSP00000338260.3
	APOL4	ENST00000616056.4	TSL:1	c.-358T>C		5_prime_UTR	Exon 1 of 6	ENSP00000483497.1
	APOL4	ENST00000449084.2	TSL:5	n.41T>C		non_coding_transcript_exon	Exon 1 of 4

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

African (AFR) AF: 0.363 AC: 893 AN: 2462

American (AMR) AF: 0.247 AC: 1118 AN: 4528

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 879 AN: 3402

East Asian (EAS) AF: 0.0239 AC: 178 AN: 7434

South Asian (SAS) AF: 0.114 AC: 1130 AN: 9902

European-Finnish (FIN) AF: 0.309 AC: 2431 AN: 7878

Middle Eastern (MID) AF: 0.345 AC: 734 AN: 2130

European-Non Finnish (NFE) AF: 0.271 AC: 18074 AN: 66590

Other (OTH) AF: 0.276 AC: 1875 AN: 6786

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

African (AFR) AF: 0.421 AC: 17390 AN: 41326

American (AMR) AF: 0.350 AC: 5337 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1134 AN: 3466

East Asian (EAS) AF: 0.0340 AC: 176 AN: 5172

South Asian (SAS) AF: 0.153 AC: 736 AN: 4810

European-Finnish (FIN) AF: 0.392 AC: 4115 AN: 10508

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

European-Non Finnish (NFE) AF: 0.350 AC: 23751 AN: 67874

Other (OTH) AF: 0.337 AC: 712 AN: 2112

Alfa AF: 0.362 Hom.: 2066

Bravo AF: 0.356

Asia WGS AF: 0.136 AC: 474 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.43
DANN	Benign	0.36
PhyloP100		-1.1
PromoterAI		0.17	Neutral
Mutation Taster		=300/0	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: rs6000189; hg19: chr22-36600814;