Variant rs7405731 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002230.4(JUP):c.213T>C(p.Asp71=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.752 in 1,606,858 control chromosomes in the GnomAD database, including 458,367 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.77 ( 45851 hom., cov: 32)

Exomes 𝑓: 0.75 ( 412516 hom. )

Consequence

JUP
NM_002230.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:16

Conservation

PhyloP100: 0.455

Variant links:

Genes affected

JUP (HGNC:6207): (junction plakoglobin) This gene encodes a major cytoplasmic protein which is the only known constituent common to submembranous plaques of both desmosomes and intermediate junctions. This protein forms distinct complexes with cadherins and desmosomal cadherins and is a member of the catenin family since it contains a distinct repeating amino acid motif called the armadillo repeat. Mutation in this gene has been associated with Naxos disease. Alternative splicing occurs in this gene; however, not all transcripts have been fully described. [provided by RefSeq, Jul 2008]

JUP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 17-41769673-A-G is Benign according to our data. Variant chr17-41769673-A-G is described in ClinVar as [Benign]. Clinvar id is 45845.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-41769673-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.455 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JUP	NM_002230.4 linkuse as main transcript	c.213T>C	p.Asp71=	synonymous_variant	3/14	ENST00000393931.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JUP	ENST00000393931.8 linkuse as main transcript	c.213T>C	p.Asp71=	synonymous_variant	3/14	1	NM_002230.4	P1

Frequencies

GnomAD3 genomes

AF:

0.771

AC:

117207

AN:

152052

Hom.:

45801

Cov.:

show subpopulations

Gnomad AFR

AF:

0.882

Gnomad AMI

AF:

0.752

Gnomad AMR

AF:

0.658

Gnomad ASJ

AF:

0.809

Gnomad EAS

AF:

0.517

Gnomad SAS

AF:

0.748

Gnomad FIN

AF:

0.670

Gnomad MID

AF:

0.829

Gnomad NFE

AF:

0.763

Gnomad OTH

AF:

0.763

GnomAD3 exomes

AF:

0.711

AC:

167306

AN:

235266

Hom.:

60982

AF XY:

0.721

AC XY:

91753

AN XY:

127262

show subpopulations

Gnomad AFR exome

AF:

0.887

Gnomad AMR exome

AF:

0.523

Gnomad ASJ exome

AF:

0.826

Gnomad EAS exome

AF:

0.511

Gnomad SAS exome

AF:

0.758

Gnomad FIN exome

AF:

0.681

Gnomad NFE exome

AF:

0.758

Gnomad OTH exome

AF:

0.734

GnomAD4 exome

AF:

0.750

AC:

1091432

AN:

1454688

Hom.:

412516

Cov.:

AF XY:

0.752

AC XY:

543348

AN XY:

722944

show subpopulations

Gnomad4 AFR exome

AF:

0.890

Gnomad4 AMR exome

AF:

0.538

Gnomad4 ASJ exome

AF:

0.816

Gnomad4 EAS exome

AF:

0.518

Gnomad4 SAS exome

AF:

0.759

Gnomad4 FIN exome

AF:

0.684

Gnomad4 NFE exome

AF:

0.763

Gnomad4 OTH exome

AF:

0.757

GnomAD4 genome

AF:

0.771

AC:

117318

AN:

152170

Hom.:

45851

Cov.:

AF XY:

0.762

AC XY:

56711

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.882

Gnomad4 AMR

AF:

0.657

Gnomad4 ASJ

AF:

0.809

Gnomad4 EAS

AF:

0.517

Gnomad4 SAS

AF:

0.750

Gnomad4 FIN

AF:

0.670

Gnomad4 NFE

AF:

0.763

Gnomad4 OTH

AF:

0.767

Alfa

AF:

0.745

Hom.:

18294

Bravo

AF:

0.770

Asia WGS

AF:

0.673

AC:

2346

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:16

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:8

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 30, 2011	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	May 17, 2016	- -

Naxos disease

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 19, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Arrhythmogenic right ventricular dysplasia 12

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 19, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Cardiomyopathy

Benign:1

Benign, no assertion criteria provided

clinical testing

Cohesion Phenomics

Sep 23, 2022

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 09, 2015

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Naxos disease;C1969081:Arrhythmogenic right ventricular dysplasia 12

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

9.5

DANN

Benign

0.52

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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