Genetic Variant ENST00000352371.5:c.-82T>C (chr22-36204690-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.-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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0170

Publications

7 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

new If you want to explore the variant's impact on the transcript ENST00000352371.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.91).

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

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
APOL4	NM_145660.2	c.-82T>C	5_prime_UTR	Exon 1 of 5	NP_663693.1	Q9BPW4-1
APOL4	NM_030643.4	c.-280T>C	5_prime_UTR	Exon 1 of 6	NP_085146.2	Q9BPW4-2
APOL4	NM_145661.2	c.-280T>C	5_prime_UTR	Exon 1 of 6	NP_663694.1	Q9BRG6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
APOL4	ENST00000352371.5	TSL:1	c.-82T>C	5_prime_UTR	Exon 1 of 5	ENSP00000338260.3	Q9BPW4-1
APOL4	ENST00000616056.4	TSL:1	c.-280T>C	5_prime_UTR	Exon 1 of 6	ENSP00000483497.1	Q9BPW4-2
APOL4	ENST00000397275.6	TSL:1	c.-280T>C	5_prime_UTR	Exon 1 of 6	ENSP00000380445.2	Q9BRG6

Frequencies

GnomAD3 genomes

AF:

0.351

AC:

50234

AN:

142996

Hom.:

7486

Cov.:

show subpopulations

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.:

AF XY:

0.285

AC XY:

64407

AN XY:

225856

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

3411

6821

10232

13642

17053

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2394

4788

7182

9576

11970

<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:

0.351

AC:

50304

AN:

143128

Hom.:

7505

Cov.:

AF XY:

0.350

AC XY:

24559

AN XY:

70150

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1535

3070

4604

6139

7674

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

506

1012

1518

2024

2530

<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:

0.360

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

(source)

DANN

Benign

0.43

PhyloP100

-0.017

PromoterAI

0.10

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over