22-36204690-A-G

Variant names:

• chr22-36204690-A-G
• rs5995250
• ENST00000352371.5:c.-82T>C

Variant summary

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

The ENST00000352371.5(APOL4):​c.-82T>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 0.307 in 572,802 control chromosomes in the GnomAD database, including 27,164 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 (7505 hom., cov: 30)
  • Exomes 𝑓: 0.29 (19659 hom.)
• Consequence: APOL4 ENST00000352371.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0170
• Publications: 7 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.409 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.-82T>C		5_prime_UTR	Exon 1 of 5	NP_663693.1
	APOL4	NM_030643.4		c.-280T>C		5_prime_UTR	Exon 1 of 6	NP_085146.2
	APOL4	NM_145661.2		c.-280T>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.-82T>C		5_prime_UTR	Exon 1 of 5	ENSP00000338260.3
	APOL4	ENST00000616056.4	TSL:1	c.-280T>C		5_prime_UTR	Exon 1 of 6	ENSP00000483497.1
	APOL4	ENST00000397275.6	TSL:1	c.-280T>C		5_prime_UTR	Exon 1 of 6	ENSP00000380445.2

Frequencies

GnomAD3 genomes AF: 0.351 AC: 50234 AN: 142996 Hom.: 7486 Cov.: 30

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.0384

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.343

GnomAD4 exome AF: 0.292 AC: 125466 AN: 429674 Hom.: 19659 Cov.: 6 AF XY: 0.285 AC XY: 64407 AN XY: 225856

African (AFR) AF: 0.389 AC: 3684 AN: 9470

American (AMR) AF: 0.284 AC: 4850 AN: 17082

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 2686 AN: 9320

East Asian (EAS) AF: 0.0274 AC: 472 AN: 17232

South Asian (SAS) AF: 0.132 AC: 4047 AN: 30586

European-Finnish (FIN) AF: 0.344 AC: 6947 AN: 20182

Middle Eastern (MID) AF: 0.340 AC: 1048 AN: 3080

European-Non Finnish (NFE) AF: 0.316 AC: 95811 AN: 302756

Other (OTH) AF: 0.297 AC: 5921 AN: 19966

GnomAD4 genome AF: 0.351 AC: 50304 AN: 143128 Hom.: 7505 Cov.: 30 AF XY: 0.350 AC XY: 24559 AN XY: 70150

African (AFR) AF: 0.414 AC: 16153 AN: 39030

American (AMR) AF: 0.345 AC: 5018 AN: 14528

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1067 AN: 3260

East Asian (EAS) AF: 0.0387 AC: 175 AN: 4520

South Asian (SAS) AF: 0.163 AC: 716 AN: 4388

European-Finnish (FIN) AF: 0.391 AC: 4009 AN: 10244

Middle Eastern (MID) AF: 0.396 AC: 103 AN: 260

European-Non Finnish (NFE) AF: 0.346 AC: 22174 AN: 64092

Other (OTH) AF: 0.339 AC: 671 AN: 1982

Alfa AF: 0.360 Hom.: 2038

Bravo AF: 0.356

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.7
DANN	Benign	0.43
PhyloP100		-0.017
PromoterAI		0.10	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: rs5995250; hg19: chr22-36600736;