rs1719013

Variant names:

• chr15-29859586-G-A
• rs1719013
• NM_001301025.3:c.307-58884C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-29859586-G-A
• chr15-29859586-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001301025.3(TJP1):​c.307-58884C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 151,868 control chromosomes in the GnomAD database, including 10,991 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.37 (10991 hom., cov: 32)
• Consequence: TJP1 NM_001301025.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.108
• Publications: 3 publications found

Genes affected

TJP1 (HGNC:11827): (tight junction protein 1) This gene encodes a member of the membrane-associated guanylate kinase (MAGUK) family of proteins, and acts as a tight junction adaptor protein that also regulates adherens junctions. Tight junctions regulate the movement of ions and macromolecules between endothelial and epithelial cells. The multidomain structure of this scaffold protein, including a postsynaptic density 95/disc-large/zona occludens (PDZ) domain, a Src homology (SH3) domain, a guanylate kinase (GuK) domain and unique (U) motifs all help to co-ordinate binding of transmembrane proteins, cytosolic proteins, and F-actin, which are required for tight junction function. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2017]

TJP1 Gene-Disease associations (from GenCC):

• arrhythmogenic right ventricular cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ENSG00000295789 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TJP1	NM_001301025.3	c.307-58884C>T		intron_variant	Intron 2 of 28		NP_001287954.2
TJP1	NM_001355012.2	c.307-58884C>T		intron_variant	Intron 2 of 28		NP_001341941.1
TJP1	XM_017022521.2	c.307-58884C>T		intron_variant	Intron 2 of 29		XP_016878010.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TJP1	ENST00000356107.11	c.307-58884C>T		intron_variant	Intron 2 of 28	5		ENSP00000348416.7
TJP1	ENST00000473741.1	n.64-58884C>T		intron_variant	Intron 1 of 1	2
ENSG00000295789	ENST00000732735.1	n.128+13141C>T		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.369 AC: 56065 AN: 151752 Hom.: 10970 Cov.: 32

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.292

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.342

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.370 AC: 56128 AN: 151868 Hom.: 10991 Cov.: 32 AF XY: 0.371 AC XY: 27570 AN XY: 74240

African (AFR) AF: 0.497 AC: 20600 AN: 41418

American (AMR) AF: 0.347 AC: 5301 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1099 AN: 3466

East Asian (EAS) AF: 0.391 AC: 2004 AN: 5122

South Asian (SAS) AF: 0.348 AC: 1670 AN: 4804

European-Finnish (FIN) AF: 0.370 AC: 3907 AN: 10558

Middle Eastern (MID) AF: 0.286 AC: 83 AN: 290

European-Non Finnish (NFE) AF: 0.302 AC: 20495 AN: 67918

Other (OTH) AF: 0.342 AC: 720 AN: 2108

Alfa AF: 0.337 Hom.: 1078

Bravo AF: 0.370

Asia WGS AF: 0.394 AC: 1367 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.5
DANN	Benign	0.61
PhyloP100		-0.11

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1719013; hg19: chr15-30151789;