dbSNP rs6000189: APOL4:c.-160T>C (chr22-36204768-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.12

Publications

5 publications found

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
APOL4	NM_145660.2 link	c.-160T>C	5_prime_UTR_variant	Exon 1 of 5	NP_663693.1
APOL4	NM_030643.4 link	c.-358T>C	5_prime_UTR_variant	Exon 1 of 6	NP_085146.2
APOL4	NM_145661.2 link	c.-358T>C	5_prime_UTR_variant	Exon 1 of 6	NP_663694.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
APOL4	ENST00000352371.5 link	c.-160T>C	5_prime_UTR_variant	Exon 1 of 5	1	ENSP00000338260.3
APOL4	ENST00000616056.4 link	c.-358T>C	5_prime_UTR_variant	Exon 1 of 6	1	ENSP00000483497.1
APOL4	ENST00000449084.2 link	n.41T>C	non_coding_transcript_exon_variant	Exon 1 of 4	5

Frequencies

GnomAD3 genomes

AF:

0.354

AC:

53626

AN:

151608

Hom.:

9947

Cov.:

show subpopulations

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.:

AF XY:

0.239

AC XY:

14275

AN XY:

59652

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

846

1691

2537

3382

4228

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

224

336

448

560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.354

AC:

53694

AN:

151726

Hom.:

9965

Cov.:

AF XY:

0.352

AC XY:

26099

AN XY:

74114

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1680

3359

5039

6718

8398

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

512

1024

1536

2048

2560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.43

(source)

DANN

Benign

0.36

PhyloP100

-1.1

PromoterAI

0.17

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over