rs6460054

chr7-73770204-T-C

Variant summary

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

The NM_001306.4(CLDN3):c.-155A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 1,154,684 control chromosomes in the GnomAD database, including 135,534 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 0.51 (20235 hom., cov: 34)
  • Exomes 𝑓: 0.48 (115299 hom.)
• Consequence: CLDN3 NM_001306.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30

Genes affected

CLDN3 (HGNC:2045): (claudin 3) Tight junctions represent one mode of cell-to-cell adhesion in epithelial or endothelial cell sheets, forming continuous seals around cells and serving as a physical barrier to prevent solutes and water from passing freely through the paracellular space. These junctions are comprised of sets of continuous networking strands in the outwardly facing cytoplasmic leaflet, with complementary grooves in the inwardly facing extracytoplasmic leaflet. The protein encoded by this intronless gene, a member of the claudin family, is an integral membrane protein and a component of tight junction strands. It is also a low-affinity receptor for Clostridium perfringens enterotoxin, and shares aa sequence similarity with a putative apoptosis-related protein found in rat. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLDN3	NM_001306.4	c.-155A>G		5_prime_UTR_variant	1/1	ENST00000395145.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLDN3	ENST00000395145.3	c.-155A>G		5_prime_UTR_variant	1/1		NM_001306.4	P1

Frequencies

GnomAD3 genomes AF: 0.513 AC: 78022 AN: 151962 Hom.: 20237 Cov.: 34

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.558

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.532

GnomAD4 exome AF: 0.477 AC: 478548 AN: 1002616 Hom.: 115299 Cov.: 14 AF XY: 0.479 AC XY: 234540 AN XY: 489274

Gnomad4 AFR exome AF: 0.565

Gnomad4 AMR exome AF: 0.542

Gnomad4 ASJ exome AF: 0.544

Gnomad4 EAS exome AF: 0.448

Gnomad4 SAS exome AF: 0.559

Gnomad4 FIN exome AF: 0.479

Gnomad4 NFE exome AF: 0.468

Gnomad4 OTH exome AF: 0.508

GnomAD4 genome AF: 0.513 AC: 78033 AN: 152068 Hom.: 20235 Cov.: 34 AF XY: 0.514 AC XY: 38246 AN XY: 74338

Gnomad4 AFR AF: 0.559

Gnomad4 AMR AF: 0.548

Gnomad4 ASJ AF: 0.553

Gnomad4 EAS AF: 0.512

Gnomad4 SAS AF: 0.548

Gnomad4 FIN AF: 0.473

Gnomad4 NFE AF: 0.480

Gnomad4 OTH AF: 0.526

Alfa AF: 0.483 Hom.: 2253

Bravo AF: 0.522

Asia WGS AF: 0.500 AC: 1728 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	6.5
Dann	Benign	0.40

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: rs6460054; hg19: chr7-73184534;