X-129648435-C-G

Variant names:

• chrX-129648435-C-G
• rs3115757
• NM_017413.5:c.*5+186G>C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_017413.5(APLN):​c.*5+186G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 111,869 control chromosomes in the GnomAD database, including 4,959 homozygotes. There are 8,531 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.26 (4959 hom., 8531 hem., cov: 23)
• Consequence: APLN NM_017413.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.219

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant X-129648435-C-G is Benign according to our data. Variant chrX-129648435-C-G is described in ClinVar as [Benign]. Clinvar id is 1257673.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APLN	NM_017413.5	c.*5+186G>C		intron_variant	Intron 2 of 2	ENST00000429967.3	NP_059109.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APLN	ENST00000429967.3	c.*5+186G>C		intron_variant	Intron 2 of 2	1	NM_017413.5	ENSP00000391800.2

Frequencies

GnomAD3 genomes AF: 0.258 AC: 28816 AN: 111816 Hom.: 4958 Cov.: 23 AF XY: 0.250 AC XY: 8495 AN XY: 34020

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.0936

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.0534

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0740

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.258 AC: 28849 AN: 111869 Hom.: 4959 Cov.: 23 AF XY: 0.250 AC XY: 8531 AN XY: 34083

Gnomad4 AFR AF: 0.599

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.0936

Gnomad4 EAS AF: 0.695

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.0534

Gnomad4 NFE AF: 0.0740

Gnomad4 OTH AF: 0.235

Alfa AF: 0.170 Hom.: 1088

Bravo AF: 0.295

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.9
DANN	Benign	0.41

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: rs3115757; hg19: chrX-128782412;