rs77529236

chr17-41767330-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002230.4(JUP):c.909+49T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00902 in 1,522,284 control chromosomes in the GnomAD database, including 1,039 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.046 (559 hom., cov: 32)
  • Exomes 𝑓: 0.0049 (480 hom.)
• Consequence: JUP NM_002230.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.211

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 17-41767330-A-G is Benign according to our data. Variant chr17-41767330-A-G is described in ClinVar as [Benign]. Clinvar id is 261477.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JUP	NM_002230.4	c.909+49T>C		intron_variant		ENST00000393931.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JUP	ENST00000393931.8	c.909+49T>C		intron_variant		1	NM_002230.4	P1
JUP	ENST00000310706.9	c.909+49T>C		intron_variant		1		P1
JUP	ENST00000393930.5	c.909+49T>C		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.0463 AC: 7043 AN: 152136 Hom.: 552 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0204

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000691

Gnomad OTH AF: 0.0339

GnomAD3 exomes AF: 0.0124 AC: 3072 AN: 246920 Hom.: 212 AF XY: 0.00925 AC XY: 1238 AN XY: 133868

Gnomad AFR exome AF: 0.166

Gnomad AMR exome AF: 0.00989

Gnomad ASJ exome AF: 0.000700

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000262

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000384

Gnomad OTH exome AF: 0.00594

GnomAD4 exome AF: 0.00486 AC: 6653 AN: 1370030 Hom.: 480 Cov.: 22 AF XY: 0.00409 AC XY: 2809 AN XY: 686602

Gnomad4 AFR exome AF: 0.162

Gnomad4 AMR exome AF: 0.0111

Gnomad4 ASJ exome AF: 0.000470

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000344

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000269

Gnomad4 OTH exome AF: 0.0122

GnomAD4 genome AF: 0.0465 AC: 7075 AN: 152254 Hom.: 559 Cov.: 32 AF XY: 0.0452 AC XY: 3362 AN XY: 74450

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.0204

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000691

Gnomad4 OTH AF: 0.0336

Alfa AF: 0.0234 Hom.: 34

Bravo AF: 0.0531

Asia WGS AF: 0.0150 AC: 53 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	4.0
Dann	Benign	0.49

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

Other links and lift over

dbSNP: rs77529236; hg19: chr17-39923582;