X-129649590-A-G

Variant names:

• chrX-129649590-A-G
• rs909657
• NM_017413.5:c.68-798T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017413.5(APLN):​c.68-798T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 110,769 control chromosomes in the GnomAD database, including 7,534 homozygotes. There are 9,600 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 (7534 hom., 9600 hem., cov: 22)
• Consequence: APLN NM_017413.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.505
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.754 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APLN	NM_017413.5	MANE Select	c.68-798T>C		intron	N/A	NP_059109.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APLN	ENST00000429967.3	TSL:1 MANE Select	c.68-798T>C		intron	N/A	ENSP00000391800.2
	ENSG00000308713	ENST00000835926.1		n.344-1933A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.304 AC: 33678 AN: 110716 Hom.: 7527 Cov.: 22

Gnomad AFR AF: 0.762

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.0939

Gnomad EAS AF: 0.699

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.0544

Gnomad MID AF: 0.126

Gnomad NFE AF: 0.0744

Gnomad OTH AF: 0.277

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.305 AC: 33730 AN: 110769 Hom.: 7534 Cov.: 22 AF XY: 0.291 AC XY: 9600 AN XY: 32991

African (AFR) AF: 0.762 AC: 22995 AN: 30160

American (AMR) AF: 0.259 AC: 2714 AN: 10489

Ashkenazi Jewish (ASJ) AF: 0.0939 AC: 248 AN: 2642

East Asian (EAS) AF: 0.699 AC: 2419 AN: 3460

South Asian (SAS) AF: 0.248 AC: 644 AN: 2599

European-Finnish (FIN) AF: 0.0544 AC: 329 AN: 6043

Middle Eastern (MID) AF: 0.115 AC: 25 AN: 217

European-Non Finnish (NFE) AF: 0.0744 AC: 3941 AN: 52961

Other (OTH) AF: 0.274 AC: 415 AN: 1517

Alfa AF: 0.159 Hom.: 3776

Bravo AF: 0.350

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.79
DANN	Benign	0.80
PhyloP100		-0.51
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs909657; hg19: chrX-128783567;