Variant 17-41757393-T-C 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_002230.4(JUP):c.2046+22A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.74 in 1,613,556 control chromosomes in the GnomAD database, including 445,436 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.77 ( 45311 hom., cov: 33)

Exomes 𝑓: 0.74 ( 400125 hom. )

Consequence

JUP
NM_002230.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.636

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 -20 ACMG points.

BP4

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

BP6

Variant 17-41757393-T-C is Benign according to our data. Variant chr17-41757393-T-C is described in ClinVar as [Benign]. Clinvar id is 261475.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-41757393-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JUP	NM_002230.4 linkuse as main transcript	c.2046+22A>G		intron_variant		ENST00000393931.8	NP_002221.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
JUP	ENST00000393931.8 linkuse as main transcript	c.2046+22A>G	intron_variant	1	NM_002230.4	ENSP00000377508	P1
JUP	ENST00000310706.9 linkuse as main transcript	c.2046+22A>G	intron_variant	1		ENSP00000311113	P1
JUP	ENST00000393930.5 linkuse as main transcript	c.2046+22A>G	intron_variant	5		ENSP00000377507	P1

Frequencies

GnomAD3 genomes

AF:

0.765

AC:

116390

AN:

152076

Hom.:

45258

Cov.:

show subpopulations

Gnomad AFR

AF:

0.890

Gnomad AMI

AF:

0.876

Gnomad AMR

AF:

0.643

Gnomad ASJ

AF:

0.695

Gnomad EAS

AF:

0.512

Gnomad SAS

AF:

0.715

Gnomad FIN

AF:

0.699

Gnomad MID

AF:

0.756

Gnomad NFE

AF:

0.753

Gnomad OTH

AF:

0.738

GnomAD3 exomes

AF:

0.697

AC:

175270

AN:

251358

Hom.:

62565

AF XY:

0.704

AC XY:

95646

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.895

Gnomad AMR exome

AF:

0.520

Gnomad ASJ exome

AF:

0.711

Gnomad EAS exome

AF:

0.502

Gnomad SAS exome

AF:

0.724

Gnomad FIN exome

AF:

0.704

Gnomad NFE exome

AF:

0.745

Gnomad OTH exome

AF:

0.701

GnomAD4 exome

AF:

0.737

AC:

1077473

AN:

1461362

Hom.:

400125

Cov.:

AF XY:

0.737

AC XY:

536140

AN XY:

727006

show subpopulations

Gnomad4 AFR exome

AF:

0.896

Gnomad4 AMR exome

AF:

0.534

Gnomad4 ASJ exome

AF:

0.708

Gnomad4 EAS exome

AF:

0.525

Gnomad4 SAS exome

AF:

0.725

Gnomad4 FIN exome

AF:

0.707

Gnomad4 NFE exome

AF:

0.752

Gnomad4 OTH exome

AF:

0.732

GnomAD4 genome

AF:

0.765

AC:

116498

AN:

152194

Hom.:

45311

Cov.:

AF XY:

0.760

AC XY:

56506

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.890

Gnomad4 AMR

AF:

0.643

Gnomad4 ASJ

AF:

0.695

Gnomad4 EAS

AF:

0.512

Gnomad4 SAS

AF:

0.715

Gnomad4 FIN

AF:

0.699

Gnomad4 NFE

AF:

0.753

Gnomad4 OTH

AF:

0.741

Alfa

AF:

0.766

Hom.:

9697

Bravo

AF:

0.763

Asia WGS

AF:

0.640

AC:

2225

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 15, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Naxos disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Arrhythmogenic right ventricular dysplasia 12

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.3

DANN

Benign

0.33

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