rs2281069

Variant names:

• chrX-129654737-A-C
• rs2281069
• NM_017413.5:c.-107T>G

Your query was ambiguous. Multiple possible variants found:

• chrX-129654737-A-C
• chrX-129654737-A-G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_017413.5(APLN):​c.-107T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000239 in 510,396 control chromosomes in the GnomAD database, including 1 homozygotes. There are 34 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 0.000081 (0 hom., 0 hem., cov: 24)
  • Exomes 𝑓: 0.00028 (1 hom. 34 hem.)
• Consequence: APLN NM_017413.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04
• Publications: 1 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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BS2: High Hemizygotes in GnomAdExome4 at 34 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APLN	NM_017413.5	c.-107T>G		5_prime_UTR_variant	Exon 1 of 3	ENST00000429967.3	NP_059109.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APLN	ENST00000429967.3	c.-107T>G		5_prime_UTR_variant	Exon 1 of 3	1	NM_017413.5	ENSP00000391800.2

Frequencies

GnomAD3 genomes AF: 0.0000808 AC: 9 AN: 111446 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00263

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000283 AC: 113 AN: 398905 Hom.: 1 Cov.: 6 AF XY: 0.000456 AC XY: 34 AN XY: 74545

African (AFR) AF: 0.00 AC: 0 AN: 9158

American (AMR) AF: 0.00 AC: 0 AN: 4591

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6550

East Asian (EAS) AF: 0.00750 AC: 112 AN: 14926

South Asian (SAS) AF: 0.00 AC: 0 AN: 7799

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 15688

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1105

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 320930

Other (OTH) AF: 0.0000551 AC: 1 AN: 18158

GnomAD4 genome AF: 0.0000807 AC: 9 AN: 111491 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 33927

African (AFR) AF: 0.00 AC: 0 AN: 30669

American (AMR) AF: 0.00 AC: 0 AN: 10791

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2636

East Asian (EAS) AF: 0.00264 AC: 9 AN: 3407

South Asian (SAS) AF: 0.00 AC: 0 AN: 2782

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6058

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 215

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52728

Other (OTH) AF: 0.00 AC: 0 AN: 1530

Alfa AF: 0.00 Hom.: 84

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.0
DANN	Benign	0.60
PhyloP100		-2.0
PromoterAI		0.080	Neutral
Mutation Taster		=300/0	polymorphism

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: rs2281069; hg19: chrX-128788714;