rs3115758

Variant names:

• chrX-129647887-C-A
• rs3115758
• NM_017413.5:c.*36G>T

Your query was ambiguous. Multiple possible variants found:

• chrX-129647887-C-A
• chrX-129647887-C-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate 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
• Publications: 10 publications found

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]

ENSG00000308713 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.755 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.*36G>T		3_prime_UTR	Exon 3 of 3	NP_059109.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APLN	ENST00000429967.3	TSL:1 MANE Select	c.*36G>T		3_prime_UTR	Exon 3 of 3	ENSP00000391800.2
	APLN	ENST00000865540.1		c.*36G>T		3_prime_UTR	Exon 3 of 3	ENSP00000535599.1
	ENSG00000308713	ENST00000835926.1		n.344-3636C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.305 AC: 33696 AN: 110607 Hom.: 7505 Cov.: 22

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

GnomAD2 exomes AF: 0.214 AC: 23450 AN: 109592 AF XY: 0.202

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 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

African (AFR) AF: 0.792 AC: 15284 AN: 19298

American (AMR) AF: 0.279 AC: 6210 AN: 22268

Ashkenazi Jewish (ASJ) AF: 0.0868 AC: 1037 AN: 11951

East Asian (EAS) AF: 0.704 AC: 6833 AN: 9709

South Asian (SAS) AF: 0.230 AC: 10969 AN: 47696

European-Finnish (FIN) AF: 0.0543 AC: 1136 AN: 20905

Middle Eastern (MID) AF: 0.115 AC: 360 AN: 3139

European-Non Finnish (NFE) AF: 0.0736 AC: 51714 AN: 702759

Other (OTH) AF: 0.166 AC: 5281 AN: 31807

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

African (AFR) AF: 0.764 AC: 23082 AN: 30226

American (AMR) AF: 0.258 AC: 2709 AN: 10519

Ashkenazi Jewish (ASJ) AF: 0.0937 AC: 247 AN: 2635

East Asian (EAS) AF: 0.690 AC: 2376 AN: 3443

South Asian (SAS) AF: 0.247 AC: 640 AN: 2592

European-Finnish (FIN) AF: 0.0563 AC: 339 AN: 6024

Middle Eastern (MID) AF: 0.120 AC: 26 AN: 217

European-Non Finnish (NFE) AF: 0.0740 AC: 3911 AN: 52820

Other (OTH) AF: 0.279 AC: 421 AN: 1507

Alfa AF: 0.159 Hom.: 13378

Bravo AF: 0.349

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.12
DANN	Benign	0.50
PhyloP100		-0.55
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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