X-129654944-A-G

Position:

• chrX-129654944-A-G

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_017413.5(APLN):​c.-314T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0373 in 133,346 control chromosomes in the GnomAD database, including 102 homozygotes. There are 1,526 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.036 (85 hom., 1204 hem., cov: 24)
  • Exomes 𝑓: 0.046 (17 hom. 322 hem.)
• Consequence: APLN NM_017413.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.76

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant X-129654944-A-G is Benign according to our data. Variant chrX-129654944-A-G is described in ClinVar as [Benign]. Clinvar id is 1272734.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APLN	NM_017413.5	c.-314T>C		5_prime_UTR_variant	1/3	ENST00000429967.3	NP_059109.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APLN	ENST00000429967.3	c.-314T>C		5_prime_UTR_variant	1/3	1	NM_017413.5	ENSP00000391800.2

Frequencies

GnomAD3 genomes AF: 0.0356 AC: 4016 AN: 112716 Hom.: 84 Cov.: 24 AF XY: 0.0344 AC XY: 1201 AN XY: 34896

Gnomad AFR AF: 0.00736

Gnomad AMI AF: 0.0161

Gnomad AMR AF: 0.0190

Gnomad ASJ AF: 0.0411

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00963

Gnomad FIN AF: 0.0802

Gnomad MID AF: 0.0167

Gnomad NFE AF: 0.0545

Gnomad OTH AF: 0.0262

GnomAD4 exome AF: 0.0463 AC: 954 AN: 20584 Hom.: 17 Cov.: 0 AF XY: 0.0568 AC XY: 322 AN XY: 5674

Gnomad4 AFR exome AF: 0.0113

Gnomad4 AMR exome AF: 0.0189

Gnomad4 ASJ exome AF: 0.0438

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00621

Gnomad4 FIN exome AF: 0.0719

Gnomad4 NFE exome AF: 0.0501

Gnomad4 OTH exome AF: 0.0404

GnomAD4 genome AF: 0.0356 AC: 4019 AN: 112762 Hom.: 85 Cov.: 24 AF XY: 0.0344 AC XY: 1204 AN XY: 34952

Gnomad4 AFR AF: 0.00735

Gnomad4 AMR AF: 0.0189

Gnomad4 ASJ AF: 0.0411

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0107

Gnomad4 FIN AF: 0.0802

Gnomad4 NFE AF: 0.0545

Gnomad4 OTH AF: 0.0259

Alfa AF: 0.0482 Hom.: 264

Bravo AF: 0.0300

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	17
DANN	Benign	0.84

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs181301686; hg19: chrX-128788921;