15-29704268-G-A

Variant names:

• chr15-29704268-G-A
• rs377130760
• NM_001330239.4:c.5106C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6 BP7 BS2

The NM_001330239.4(TJP1):​c.5106C>T​(p.Pro1702Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000644 in 1,598,932 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000064 (3 hom.)
• Consequence: TJP1 NM_001330239.4 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.82
• Publications: 1 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]

LCIIAR (HGNC:56346): (lung cancer immune cell infiltration associated lncRNA)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 15-29704268-G-A is Benign according to our data. Variant chr15-29704268-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3035457.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=1.82 with no splicing effect.
• BS2: High AC in GnomAd4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TJP1	NM_001330239.4	c.5106C>T	p.Pro1702Pro	synonymous_variant	Exon 27 of 28	ENST00000614355.5	NP_001317168.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TJP1	ENST00000614355.5	c.5106C>T	p.Pro1702Pro	synonymous_variant	Exon 27 of 28	5	NM_001330239.4	ENSP00000483470.2

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152190 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000711 AC: 16 AN: 225006 AF XY: 0.0000744

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000190

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000423

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000643 AC: 93 AN: 1446742 Hom.: 3 Cov.: 31 AF XY: 0.0000530 AC XY: 38 AN XY: 717492

African (AFR) AF: 0.00 AC: 0 AN: 33394

American (AMR) AF: 0.000142 AC: 6 AN: 42308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25720

East Asian (EAS) AF: 0.000330 AC: 13 AN: 39354

South Asian (SAS) AF: 0.0000242 AC: 2 AN: 82698

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52444

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1105096

Other (OTH) AF: 0.00117 AC: 70 AN: 59978

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152190 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74350

African (AFR) AF: 0.00 AC: 0 AN: 41456

American (AMR) AF: 0.000131 AC: 2 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000498 Hom.: 1

Bravo AF: 0.000113

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

TJP1-related disorder Benign:1

Feb 20, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	8.5
DANN	Benign	0.66
PhyloP100		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs377130760; hg19: chr15-29996472;