rs17683205

chr15-29709124-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001330239.4(TJP1):c.4373-88G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 1,310,008 control chromosomes in the GnomAD database, including 8,799 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 0.10 (869 hom., cov: 32)
  • Exomes 𝑓: 0.11 (7930 hom.)
• Consequence: TJP1 NM_001330239.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.60

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TJP1	NM_001330239.4	c.4373-88G>A		intron_variant		ENST00000614355.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TJP1	ENST00000614355.5	c.4373-88G>A		intron_variant		5	NM_001330239.4	P2

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15513 AN: 152002 Hom.: 868 Cov.: 32

Gnomad AFR AF: 0.0674

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.0937

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.124

GnomAD4 exome AF: 0.111 AC: 128059 AN: 1157888 Hom.: 7930 AF XY: 0.114 AC XY: 66165 AN XY: 578788

Gnomad4 AFR exome AF: 0.0661

Gnomad4 AMR exome AF: 0.156

Gnomad4 ASJ exome AF: 0.110

Gnomad4 EAS exome AF: 0.0861

Gnomad4 SAS exome AF: 0.230

Gnomad4 FIN exome AF: 0.0985

Gnomad4 NFE exome AF: 0.102

Gnomad4 OTH exome AF: 0.119

GnomAD4 genome AF: 0.102 AC: 15509 AN: 152120 Hom.: 869 Cov.: 32 AF XY: 0.103 AC XY: 7688 AN XY: 74374

Gnomad4 AFR AF: 0.0673

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.126

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.0937

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.125

Alfa AF: 0.102 Hom.: 186

Bravo AF: 0.102

Asia WGS AF: 0.184 AC: 640 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.097
Dann	Benign	0.63

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: rs17683205; hg19: chr15-30001328; COSMIC: COSV62043696; COSMIC: COSV62043696;