Genetic Variant APLN:c.*384G>A (chrX-129647539-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_017413.5(APLN):c.*384G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 886,214 control chromosomes in the GnomAD database, including 16,081 homozygotes. There are 35,905 hemizygotes in GnomAD. 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 0.30 ( 7504 hom., 9415 hem., cov: 22)

Exomes 𝑓: 0.11 ( 8577 hom. 26490 hem. )

Consequence

APLN
NM_017413.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.250

Publications

8 publications found

Variant links:

Genes affected

APLN (HGNC:16665): (apelin) This gene encodes a peptide that functions as an endogenous ligand for the G-protein coupled apelin receptor. The encoded preproprotein is proteolytically processed into biologically active C-terminal peptide fragments. These peptide fragments activate different tissue specific signaling pathways that regulate diverse biological functions including fluid homeostasis, cardiovascular function and insulin secretion. This protein also functions as a coreceptor for the human immunodeficiency virus 1. [provided by RefSeq, Feb 2016]

APLN links:

ENSG00000308713 (HGNC:):

ENSG00000308713 links:

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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=-0.86).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017413.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APLN	NM_017413.5	MANE Select	c.*384G>A		3_prime_UTR	Exon 3 of 3	NP_059109.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
APLN	ENST00000429967.3	TSL:1 MANE Select	c.*384G>A	3_prime_UTR	Exon 3 of 3	ENSP00000391800.2	Q9ULZ1
APLN	ENST00000865540.1		c.*384G>A	3_prime_UTR	Exon 3 of 3	ENSP00000535599.1
ENSG00000308713	ENST00000835926.1		n.344-3984C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.303

AC:

33447

AN:

110511

Hom.:

7498

Cov.:

show subpopulations

Gnomad AFR

AF:

0.761

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.257

Gnomad ASJ

AF:

0.0959

Gnomad EAS

AF:

0.692

Gnomad SAS

AF:

0.243

Gnomad FIN

AF:

0.0528

Gnomad MID

AF:

0.131

Gnomad NFE

AF:

0.0742

Gnomad OTH

AF:

0.279

GnomAD4 exome

AF:

0.113

AC:

87635

AN:

775649

Hom.:

8577

Cov.:

AF XY:

0.118

AC XY:

26490

AN XY:

224487

show subpopulations

African (AFR)

AF:

0.795

AC:

13536

AN:

17024

American (AMR)

AF:

0.275

AC:

4773

AN:

17382

Ashkenazi Jewish (ASJ)

AF:

0.0852

AC:

714

AN:

8385

East Asian (EAS)

AF:

0.706

AC:

6434

AN:

9117

South Asian (SAS)

AF:

0.233

AC:

9274

AN:

39884

European-Finnish (FIN)

AF:

0.0548

AC:

975

AN:

17782

Middle Eastern (MID)

AF:

0.106

AC:

187

AN:

1763

European-Non Finnish (NFE)

AF:

0.0741

AC:

47119

AN:

636219

Other (OTH)

AF:

0.165

AC:

4623

AN:

28093

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

2181

4361

6542

8722

10903

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2532

5064

7596

10128

12660

<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:

0.303

AC:

33501

AN:

110565

Hom.:

7504

Cov.:

AF XY:

0.287

AC XY:

9415

AN XY:

32857

show subpopulations

African (AFR)

AF:

0.761

AC:

22876

AN:

30057

American (AMR)

AF:

0.257

AC:

2670

AN:

10391

Ashkenazi Jewish (ASJ)

AF:

0.0959

AC:

253

AN:

2639

East Asian (EAS)

AF:

0.692

AC:

2375

AN:

3433

South Asian (SAS)

AF:

0.243

AC:

635

AN:

2613

European-Finnish (FIN)

AF:

0.0528

AC:

318

AN:

6020

Middle Eastern (MID)

AF:

0.121

AC:

AN:

215

European-Non Finnish (NFE)

AF:

0.0742

AC:

3934

AN:

53011

Other (OTH)

AF:

0.276

AC:

414

AN:

1501

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

456

912

1368

1824

2280

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

290

580

870

1160

1450

<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:

0.185

Hom.:

7487

Bravo

AF:

0.350

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.81

(source)

DANN

Benign

0.71

PhyloP100

0.25

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over