X-129649590-A-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APLN	NM_017413.5	c.68-798T>C		intron_variant	Intron 1 of 2	ENST00000429967.3	NP_059109.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APLN	ENST00000429967.3	c.68-798T>C		intron_variant	Intron 1 of 2	1	NM_017413.5	ENSP00000391800.2

Frequencies

GnomAD3 genomes AF: 0.304 AC: 33678 AN: 110716 Hom.: 7527 Cov.: 22 AF XY: 0.290 AC XY: 9553 AN XY: 32928

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

Gnomad4 AFR AF: 0.762

Gnomad4 AMR AF: 0.259

Gnomad4 ASJ AF: 0.0939

Gnomad4 EAS AF: 0.699

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.0544

Gnomad4 NFE AF: 0.0744

Gnomad4 OTH AF: 0.274

Alfa AF: 0.150 Hom.: 3147

Bravo AF: 0.350

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.79
DANN	Benign	0.80

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

Other links and lift over

dbSNP: rs909657; hg19: chrX-128783567;