rs1719013

chr15-29859586-G-Achr15-29859586-G-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
TJP1	NM_001301025.3	c.307-58884C>T		intron_variant
TJP1	NM_001355012.2	c.307-58884C>T		intron_variant
TJP1	XM_005254619.4	c.307-58884C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TJP1	ENST00000356107.11	c.307-58884C>T		intron_variant		5		A2
TJP1	ENST00000473741.1	n.64-58884C>T		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.497

Gnomad4 AMR AF: 0.347

Gnomad4 ASJ AF: 0.317

Gnomad4 EAS AF: 0.391

Gnomad4 SAS AF: 0.348

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.302

Gnomad4 OTH AF: 0.342

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1719013; hg19: chr15-30151789;