Variant X-129648559-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017413.5(APLN):c.*5+62C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0569 in 1,128,868 control chromosomes in the GnomAD database, including 4,865 homozygotes. There are 20,182 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1456 hom., 4458 hem., cov: 24)

Exomes 𝑓: 0.049 ( 3409 hom. 15724 hem. )

Consequence

APLN
NM_017413.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.648

Variant links:

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]

APLN links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant X-129648559-G-A is Benign according to our data. Variant chrX-129648559-G-A is described in ClinVar as [Benign]. Clinvar id is 1275609.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APLN	NM_017413.5 linkuse as main transcript	c.*5+62C>T		intron_variant		ENST00000429967.3	NP_059109.3	Q9ULZ1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APLN	ENST00000429967.3 linkuse as main transcript	c.*5+62C>T		intron_variant		1	NM_017413.5	ENSP00000391800.2		Q9ULZ1

Frequencies

GnomAD3 genomes

AF:

0.129

AC:

14519

AN:

112908

Hom.:

1455

Cov.:

AF XY:

0.127

AC XY:

4445

AN XY:

35076

show subpopulations

Gnomad AFR

AF:

0.310

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.119

Gnomad ASJ

AF:

0.00641

Gnomad EAS

AF:

0.460

Gnomad SAS

AF:

0.113

Gnomad FIN

AF:

0.0256

Gnomad MID

AF:

0.0714

Gnomad NFE

AF:

0.0244

Gnomad OTH

AF:

0.117

GnomAD4 exome

AF:

0.0489

AC:

49713

AN:

1015909

Hom.:

3409

AF XY:

0.0502

AC XY:

15724

AN XY:

313245

show subpopulations

Gnomad4 AFR exome

AF:

0.324

Gnomad4 AMR exome

AF:

0.131

Gnomad4 ASJ exome

AF:

0.00951

Gnomad4 EAS exome

AF:

0.435

Gnomad4 SAS exome

AF:

0.105

Gnomad4 FIN exome

AF:

0.0261

Gnomad4 NFE exome

AF:

0.0226

Gnomad4 OTH exome

AF:

0.0707

GnomAD4 genome

AF:

0.129

AC:

14536

AN:

112959

Hom.:

1456

Cov.:

AF XY:

0.127

AC XY:

4458

AN XY:

35137

show subpopulations

Gnomad4 AFR

AF:

0.310

Gnomad4 AMR

AF:

0.119

Gnomad4 ASJ

AF:

0.00641

Gnomad4 EAS

AF:

0.460

Gnomad4 SAS

AF:

0.113

Gnomad4 FIN

AF:

0.0256

Gnomad4 NFE

AF:

0.0244

Gnomad4 OTH

AF:

0.115

Alfa

AF:

0.0221

Hom.:

113

Bravo

AF:

0.150

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

-0.89

CADD

Benign

0.43

DANN

Benign

0.62

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over