rs3115758

Positions:

• chrX-129647887-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017413.5(APLN):​c.*36G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 980,193 control chromosomes in the GnomAD database, including 16,837 homozygotes. There are 42,482 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 (7511 hom., 9661 hem., cov: 22)
  • Exomes 𝑓: 0.11 (9326 hom. 32821 hem.)
• Consequence: APLN NM_017413.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.550

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APLN	NM_017413.5	c.*36G>T		3_prime_UTR_variant	3/3	ENST00000429967.3	NP_059109.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APLN	ENST00000429967.3	c.*36G>T		3_prime_UTR_variant	3/3	1	NM_017413.5	ENSP00000391800	P1

Frequencies

GnomAD3 genomes AF: 0.305 AC: 33696 AN: 110607 Hom.: 7505 Cov.: 22 AF XY: 0.293 AC XY: 9610 AN XY: 32853

Gnomad AFR AF: 0.763

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.0937

Gnomad EAS AF: 0.690

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.0563

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0741

Gnomad OTH AF: 0.283

GnomAD3 exomes AF: 0.214 AC: 23450 AN: 109592 Hom.: 3478 AF XY: 0.202 AC XY: 8099 AN XY: 40042

Gnomad AFR exome AF: 0.790

Gnomad AMR exome AF: 0.278

Gnomad ASJ exome AF: 0.0871

Gnomad EAS exome AF: 0.712

Gnomad SAS exome AF: 0.233

Gnomad FIN exome AF: 0.0538

Gnomad NFE exome AF: 0.0748

Gnomad OTH exome AF: 0.157

GnomAD4 exome AF: 0.114 AC: 98824 AN: 869532 Hom.: 9326 Cov.: 31 AF XY: 0.116 AC XY: 32821 AN XY: 282360

Gnomad4 AFR exome AF: 0.792

Gnomad4 AMR exome AF: 0.279

Gnomad4 ASJ exome AF: 0.0868

Gnomad4 EAS exome AF: 0.704

Gnomad4 SAS exome AF: 0.230

Gnomad4 FIN exome AF: 0.0543

Gnomad4 NFE exome AF: 0.0736

Gnomad4 OTH exome AF: 0.166

GnomAD4 genome AF: 0.305 AC: 33751 AN: 110661 Hom.: 7511 Cov.: 22 AF XY: 0.293 AC XY: 9661 AN XY: 32917

Gnomad4 AFR AF: 0.764

Gnomad4 AMR AF: 0.258

Gnomad4 ASJ AF: 0.0937

Gnomad4 EAS AF: 0.690

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.0563

Gnomad4 NFE AF: 0.0740

Gnomad4 OTH AF: 0.279

Alfa AF: 0.118 Hom.: 6384

Bravo AF: 0.349

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.12
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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

Other links and lift over

dbSNP: rs3115758; hg19: chrX-128781864; COSMIC: COSV56741793;