chrX-129653118-A-G

Position:

• chrX-129653118-A-G

Variant summary

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

The NM_017413.5(APLN):​c.67+1446T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 111,529 control chromosomes in the GnomAD database, including 7,526 homozygotes. There are 9,990 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 0.31 (7526 hom., 9990 hem., cov: 23)
• Consequence: APLN NM_017413.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780

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=-0.87).
• 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.67+1446T>C		intron_variant		ENST00000429967.3	NP_059109.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APLN	ENST00000429967.3	c.67+1446T>C		intron_variant		1	NM_017413.5	ENSP00000391800.2

Frequencies

GnomAD3 genomes AF: 0.305 AC: 34028 AN: 111473 Hom.: 7519 Cov.: 23 AF XY: 0.295 AC XY: 9942 AN XY: 33731

Gnomad AFR AF: 0.763

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.0917

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.0524

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.0743

Gnomad OTH AF: 0.284

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

GnomAD4 genome AF: 0.306 AC: 34081 AN: 111529 Hom.: 7526 Cov.: 23 AF XY: 0.296 AC XY: 9990 AN XY: 33797

Gnomad4 AFR AF: 0.763

Gnomad4 AMR AF: 0.258

Gnomad4 ASJ AF: 0.0917

Gnomad4 EAS AF: 0.695

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.0524

Gnomad4 NFE AF: 0.0743

Gnomad4 OTH AF: 0.281

Alfa AF: 0.122 Hom.: 6782

Bravo AF: 0.350

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.0
DANN	Benign	0.34

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: rs2235312; hg19: chrX-128787095;