X-129648435-C-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 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 -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017413.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APLN	NM_017413.5	MANE Select	c.*5+186G>C		intron	N/A	NP_059109.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APLN	ENST00000429967.3	TSL:1 MANE Select	c.*5+186G>C		intron	N/A	ENSP00000391800.2	Q9ULZ1
	APLN	ENST00000865540.1		c.*5+186G>C		intron	N/A	ENSP00000535599.1
	ENSG00000308713	ENST00000835926.1		n.344-3088C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.258 AC: 28816 AN: 111816 Hom.: 4958 Cov.: 23

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

African (AFR) AF: 0.599 AC: 18346 AN: 30653

American (AMR) AF: 0.237 AC: 2530 AN: 10677

Ashkenazi Jewish (ASJ) AF: 0.0936 AC: 248 AN: 2649

East Asian (EAS) AF: 0.695 AC: 2430 AN: 3494

South Asian (SAS) AF: 0.240 AC: 653 AN: 2718

European-Finnish (FIN) AF: 0.0534 AC: 328 AN: 6142

Middle Eastern (MID) AF: 0.116 AC: 25 AN: 215

European-Non Finnish (NFE) AF: 0.0740 AC: 3929 AN: 53108

Other (OTH) AF: 0.235 AC: 360 AN: 1530

Alfa AF: 0.170 Hom.: 1088

Bravo AF: 0.295

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.9
DANN	Benign	0.41
PhyloP100		-0.22
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: rs3115757; hg19: chrX-128782412;