X-129650855-C-T

Variant names:

• chrX-129650855-C-T
• rs2235307
• NM_017413.5:c.68-2063G>A

Variant summary

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

The NM_017413.5(APLN):​c.68-2063G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0937 in 111,344 control chromosomes in the GnomAD database, including 567 homozygotes. There are 2,855 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 0.094 (567 hom., 2855 hem., cov: 23)
• Consequence: APLN NM_017413.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0290
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APLN	NM_017413.5	MANE Select	c.68-2063G>A		intron	N/A	NP_059109.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APLN	ENST00000429967.3	TSL:1 MANE Select	c.68-2063G>A		intron	N/A	ENSP00000391800.2
	ENSG00000308713	ENST00000835926.1		n.344-668C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0936 AC: 10421 AN: 111289 Hom.: 567 Cov.: 23

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0784

Gnomad ASJ AF: 0.0695

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0241

Gnomad MID AF: 0.0549

Gnomad NFE AF: 0.0479

Gnomad OTH AF: 0.0973

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

GnomAD4 genome AF: 0.0937 AC: 10432 AN: 111344 Hom.: 567 Cov.: 23 AF XY: 0.0850 AC XY: 2855 AN XY: 33582

African (AFR) AF: 0.185 AC: 5667 AN: 30551

American (AMR) AF: 0.0781 AC: 824 AN: 10546

Ashkenazi Jewish (ASJ) AF: 0.0695 AC: 184 AN: 2648

East Asian (EAS) AF: 0.179 AC: 624 AN: 3489

South Asian (SAS) AF: 0.111 AC: 290 AN: 2619

European-Finnish (FIN) AF: 0.0241 AC: 146 AN: 6064

Middle Eastern (MID) AF: 0.0602 AC: 13 AN: 216

European-Non Finnish (NFE) AF: 0.0479 AC: 2538 AN: 53004

Other (OTH) AF: 0.0960 AC: 146 AN: 1521

Alfa AF: 0.0506 Hom.: 1525

Bravo AF: 0.104

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.72
DANN	Benign	0.34
PhyloP100		-0.029
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: rs2235307; hg19: chrX-128784832;