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

Variant summary

Our verdict is Benign. Variant got -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

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 made for transcript

Verdict is Benign. Variant got -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 id 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.:

AF XY:

0.133

AC XY:

4494

AN XY:

33862

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

Gnomad4 AFR exome

AF:

0.363

Gnomad4 AMR exome

AF:

0.0941

Gnomad4 ASJ exome

AF:

0.0654

Gnomad4 EAS exome

AF:

0.316

Gnomad4 SAS exome

AF:

0.143

Gnomad4 FIN exome

AF:

0.0461

Gnomad4 NFE exome

AF:

0.0583

Gnomad4 OTH exome

AF:

0.108

GnomAD4 genome

AF:

0.143

AC:

15994

AN:

111457

Hom.:

1535

Cov.:

AF XY:

0.133

AC XY:

4505

AN XY:

33915

show subpopulations

Gnomad4 AFR

AF:

0.331

Gnomad4 AMR

AF:

0.0997

Gnomad4 ASJ

AF:

0.0744

Gnomad4 EAS

AF:

0.317

Gnomad4 SAS

AF:

0.120

Gnomad4 FIN

AF:

0.0462

Gnomad4 NFE

AF:

0.0503

Gnomad4 OTH

AF:

0.141

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

DANN

Benign

0.57

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over