rs2235306

Variant names:

• chrX-129650121-T-C
• rs2235306
• NM_017413.5:c.68-1329A>G

Variant summary

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

The NM_017413.5(APLN):​c.68-1329A>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
• Publications: 13 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=-0.83).
• 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 rank	MANE	Protein	UniProt
APLN	NM_017413.5	c.68-1329A>G		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.68-1329A>G		intron_variant	Intron 1 of 2	1	NM_017413.5	ENSP00000391800.2
ENSG00000308713	ENST00000835926.1	n.344-1402T>C		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.123 AC: 13590 AN: 110203 Hom.: 1346 Cov.: 21

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

African (AFR) AF: 0.295 AC: 8875 AN: 30103

American (AMR) AF: 0.116 AC: 1205 AN: 10409

Ashkenazi Jewish (ASJ) AF: 0.00684 AC: 18 AN: 2632

East Asian (EAS) AF: 0.464 AC: 1588 AN: 3422

South Asian (SAS) AF: 0.119 AC: 304 AN: 2563

European-Finnish (FIN) AF: 0.0270 AC: 159 AN: 5895

Middle Eastern (MID) AF: 0.0566 AC: 12 AN: 212

European-Non Finnish (NFE) AF: 0.0243 AC: 1282 AN: 52835

Other (OTH) AF: 0.109 AC: 164 AN: 1503

Alfa AF: 0.0522 Hom.: 945

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
PhyloP100		0.30
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: rs2235306; hg19: chrX-128784098; COSMIC: COSV56741809;