rs785422

Positions:

• chr15-29881682-C-T

Variant summary

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

The NM_001301025.3(TJP1):​c.306+74550G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0986 in 152,130 control chromosomes in the GnomAD database, including 804 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 0.099 (804 hom., cov: 32)
• Consequence: TJP1 NM_001301025.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.457

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TJP1	NM_001301025.3	c.306+74550G>A		intron_variant
TJP1	NM_001355012.2	c.306+74550G>A		intron_variant
TJP1	XM_005254619.4	c.306+74550G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TJP1	ENST00000356107.11	c.306+74550G>A		intron_variant		5		A2
TJP1	ENST00000473741.1	n.63+74550G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0987 AC: 15004 AN: 152012 Hom.: 804 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.0796

Gnomad ASJ AF: 0.0988

Gnomad EAS AF: 0.00867

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0648

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.0967

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

GnomAD4 genome AF: 0.0986 AC: 15007 AN: 152130 Hom.: 804 Cov.: 32 AF XY: 0.0957 AC XY: 7122 AN XY: 74384

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.0794

Gnomad4 ASJ AF: 0.0988

Gnomad4 EAS AF: 0.00849

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.0648

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.0956

Alfa AF: 0.106 Hom.: 1188

Bravo AF: 0.0994

Asia WGS AF: 0.0690 AC: 240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.8
DANN	Benign	0.56

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs785422; hg19: chr15-30173885;