X-129654413-T-C

Variant names:

• chrX-129654413-T-C
• rs5977130
• NM_017413.5:c.67+151A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_017413.5(APLN):​c.67+151A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 423,608 control chromosomes in the GnomAD database, including 13,784 homozygotes. There are 23,308 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (7145 hom., 10181 hem., cov: 24)
  • Exomes 𝑓: 0.15 (6639 hom. 13127 hem.)
• Consequence: APLN NM_017413.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.218
• Publications: 0 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant X-129654413-T-C is Benign according to our data. Variant chrX-129654413-T-C is described in ClinVar as Benign. ClinVar VariationId is 1253078.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.787 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.67+151A>G		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.67+151A>G		intron	N/A	ENSP00000391800.2	Q9ULZ1
	APLN	ENST00000865540.1		c.218A>G	p.Glu73Gly	missense	Exon 1 of 3	ENSP00000535599.1

Frequencies

GnomAD3 genomes AF: 0.301 AC: 33759 AN: 112117 Hom.: 7138 Cov.: 24

Gnomad AFR AF: 0.728

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.0979

Gnomad EAS AF: 0.812

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.0530

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0755

Gnomad OTH AF: 0.285

GnomAD4 exome AF: 0.147 AC: 45757 AN: 311441 Hom.: 6639 AF XY: 0.167 AC XY: 13127 AN XY: 78747

African (AFR) AF: 0.736 AC: 5311 AN: 7214

American (AMR) AF: 0.269 AC: 1663 AN: 6176

Ashkenazi Jewish (ASJ) AF: 0.0864 AC: 635 AN: 7350

East Asian (EAS) AF: 0.794 AC: 13642 AN: 17183

South Asian (SAS) AF: 0.253 AC: 3488 AN: 13761

European-Finnish (FIN) AF: 0.0521 AC: 964 AN: 18495

Middle Eastern (MID) AF: 0.0996 AC: 111 AN: 1114

European-Non Finnish (NFE) AF: 0.0745 AC: 16653 AN: 223402

Other (OTH) AF: 0.196 AC: 3290 AN: 16746

GnomAD4 genome AF: 0.301 AC: 33807 AN: 112167 Hom.: 7145 Cov.: 24 AF XY: 0.296 AC XY: 10181 AN XY: 34453

African (AFR) AF: 0.728 AC: 22467 AN: 30864

American (AMR) AF: 0.258 AC: 2795 AN: 10840

Ashkenazi Jewish (ASJ) AF: 0.0979 AC: 259 AN: 2645

East Asian (EAS) AF: 0.812 AC: 2805 AN: 3454

South Asian (SAS) AF: 0.249 AC: 696 AN: 2800

European-Finnish (FIN) AF: 0.0530 AC: 327 AN: 6172

Middle Eastern (MID) AF: 0.119 AC: 26 AN: 218

European-Non Finnish (NFE) AF: 0.0755 AC: 3998 AN: 52956

Other (OTH) AF: 0.282 AC: 434 AN: 1538

Alfa AF: 0.171 Hom.: 1423

Bravo AF: 0.343

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	13
DANN	Benign	0.71
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: rs5977130; hg19: chrX-128788390;