rs2235306

Positions:

• chrX-129650121-T-C

Variant summary

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

The NM_017413.5(APLN):​c.68-1329A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 110,256 control chromosomes in the GnomAD database, including 1,347 homozygotes. There are 3,875 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 0.12 (1347 hom., 3875 hem., cov: 21)
• Consequence: APLN NM_017413.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.300

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APLN	NM_017413.5	c.68-1329A>G		intron_variant		ENST00000429967.3	NP_059109.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APLN	ENST00000429967.3	c.68-1329A>G		intron_variant		1	NM_017413.5	ENSP00000391800	P1

Frequencies

GnomAD3 genomes AF: 0.123 AC: 13590 AN: 110203 Hom.: 1346 Cov.: 21 AF XY: 0.119 AC XY: 3861 AN XY: 32511

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.00684

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.0270

Gnomad MID AF: 0.0644

Gnomad NFE AF: 0.0243

Gnomad OTH AF: 0.111

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

GnomAD4 genome AF: 0.123 AC: 13607 AN: 110256 Hom.: 1347 Cov.: 21 AF XY: 0.119 AC XY: 3875 AN XY: 32574

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.00684

Gnomad4 EAS AF: 0.464

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.0270

Gnomad4 NFE AF: 0.0243

Gnomad4 OTH AF: 0.109

Alfa AF: 0.0542 Hom.: 885

Bravo AF: 0.145

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.9
DANN	Benign	0.65

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: rs2235306; hg19: chrX-128784098; COSMIC: COSV56741809;