Genetic Variant APLN:c.-107T>C (chrX-129654737-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017413.5(APLN):c.-107T>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 0.093 in 509,770 control chromosomes in the GnomAD database, including 3,124 homozygotes. There are 12,289 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1535 hom., 4505 hem., cov: 24)

Exomes 𝑓: 0.079 ( 1589 hom. 7784 hem. )

Consequence

APLN
NM_017413.5 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.04

Publications

1 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant X-129654737-A-G is Benign according to our data. Variant chrX-129654737-A-G is described in ClinVar as Benign. ClinVar VariationId is 1264640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APLN	NM_017413.5 link	c.-107T>C		5_prime_UTR_variant	Exon 1 of 3	ENST00000429967.3	NP_059109.3	Q9ULZ1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APLN	ENST00000429967.3 link	c.-107T>C		5_prime_UTR_variant	Exon 1 of 3	1	NM_017413.5	ENSP00000391800.2		Q9ULZ1

Frequencies

GnomAD3 genomes

AF:

0.143

AC:

15977

AN:

111412

Hom.:

1532

Cov.:

show subpopulations

Gnomad AFR

AF:

0.331

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.100

Gnomad ASJ

AF:

0.0744

Gnomad EAS

AF:

0.316

Gnomad SAS

AF:

0.119

Gnomad FIN

AF:

0.0462

Gnomad MID

AF:

0.0549

Gnomad NFE

AF:

0.0503

Gnomad OTH

AF:

0.142

GnomAD4 exome

AF:

0.0788

AC:

31396

AN:

398313

Hom.:

1589

Cov.:

AF XY:

0.104

AC XY:

7784

AN XY:

74531

show subpopulations

African (AFR)

AF:

0.363

AC:

3310

AN:

9118

American (AMR)

AF:

0.0941

AC:

431

AN:

4581

Ashkenazi Jewish (ASJ)

AF:

0.0654

AC:

428

AN:

6540

East Asian (EAS)

AF:

0.316

AC:

4686

AN:

14830

South Asian (SAS)

AF:

0.143

AC:

1113

AN:

7775

European-Finnish (FIN)

AF:

0.0461

AC:

723

AN:

15670

Middle Eastern (MID)

AF:

0.0624

AC:

AN:

1105

European-Non Finnish (NFE)

AF:

0.0583

AC:

18682

AN:

320564

Other (OTH)

AF:

0.108

AC:

1954

AN:

18130

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

912

1824

2735

3647

4559

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

810

1620

2430

3240

4050

<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:

0.143

AC:

15994

AN:

111457

Hom.:

1535

Cov.:

AF XY:

0.133

AC XY:

4505

AN XY:

33915

show subpopulations

African (AFR)

AF:

0.331

AC:

10152

AN:

30644

American (AMR)

AF:

0.0997

AC:

1075

AN:

10787

Ashkenazi Jewish (ASJ)

AF:

0.0744

AC:

196

AN:

2636

East Asian (EAS)

AF:

0.317

AC:

1079

AN:

3407

South Asian (SAS)

AF:

0.120

AC:

333

AN:

2782

European-Finnish (FIN)

AF:

0.0462

AC:

280

AN:

6055

Middle Eastern (MID)

AF:

0.0558

AC:

AN:

215

European-Non Finnish (NFE)

AF:

0.0503

AC:

2651

AN:

52726

Other (OTH)

AF:

0.141

AC:

216

AN:

1530

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

443

887

1330

1774

2217

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

312

468

624

780

<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:

0.0163

Hom.:

Bravo

AF:

0.161

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

7.2

(source)

DANN

Benign

0.57

PhyloP100

-2.0

PromoterAI

0.018

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over