rs2235312

Variant names:

• chrX-129653118-A-G
• rs2235312
• NM_017413.5:c.67+1446T>C

Variant summary

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

The NM_017413.5(APLN):​c.67+1446T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 111,529 control chromosomes in the GnomAD database, including 7,526 homozygotes. There are 9,990 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 0.31 (7526 hom., 9990 hem., cov: 23)
• Consequence: APLN NM_017413.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.755 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.67+1446T>C		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.67+1446T>C		intron	N/A	ENSP00000391800.2

Frequencies

GnomAD3 genomes AF: 0.305 AC: 34028 AN: 111473 Hom.: 7519 Cov.: 23

Gnomad AFR AF: 0.763

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.0917

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.0524

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.0743

Gnomad OTH AF: 0.284

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

GnomAD4 genome AF: 0.306 AC: 34081 AN: 111529 Hom.: 7526 Cov.: 23 AF XY: 0.296 AC XY: 9990 AN XY: 33797

African (AFR) AF: 0.763 AC: 23293 AN: 30527

American (AMR) AF: 0.258 AC: 2740 AN: 10612

Ashkenazi Jewish (ASJ) AF: 0.0917 AC: 242 AN: 2638

East Asian (EAS) AF: 0.695 AC: 2419 AN: 3480

South Asian (SAS) AF: 0.251 AC: 668 AN: 2666

European-Finnish (FIN) AF: 0.0524 AC: 321 AN: 6123

Middle Eastern (MID) AF: 0.124 AC: 27 AN: 218

European-Non Finnish (NFE) AF: 0.0743 AC: 3939 AN: 53041

Other (OTH) AF: 0.281 AC: 432 AN: 1538

Alfa AF: 0.163 Hom.: 14031

Bravo AF: 0.350

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.0
DANN	Benign	0.34
PhyloP100		-0.078
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: rs2235312; hg19: chrX-128787095;