rs2717701

Positions:

• chr16-3016167-G-C

Variant summary

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

The NM_021195.5(CLDN6):​c.-21-125C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 813,862 control chromosomes in the GnomAD database, including 58,055 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 0.36 (10078 hom., cov: 33)
  • Exomes 𝑓: 0.37 (47977 hom.)
• Consequence: CLDN6 NM_021195.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.811

Genes affected

CLDN6 (HGNC:2048): (claudin 6) 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. This gene encodes a component of tight junction strands, which is a member of the claudin family. The protein is an integral membrane protein and is one of the entry cofactors for hepatitis C virus. The gene methylation may be involved in esophageal tumorigenesis. This gene is adjacent to another family member CLDN9 on chromosome 16.[provided by RefSeq, Aug 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLDN6	NM_021195.5	c.-21-125C>G		intron_variant		ENST00000328796.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLDN6	ENST00000328796.5	c.-21-125C>G		intron_variant		1	NM_021195.5	P1
CLDN6	ENST00000396925.1	c.-21-125C>G		intron_variant		5		P1
CLDN6	ENST00000572154.1	c.-21-125C>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54273 AN: 152014 Hom.: 10071 Cov.: 33

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.366

GnomAD4 exome AF: 0.374 AC: 247547 AN: 661730 Hom.: 47977 AF XY: 0.371 AC XY: 125049 AN XY: 337068

Gnomad4 AFR exome AF: 0.304

Gnomad4 AMR exome AF: 0.385

Gnomad4 ASJ exome AF: 0.417

Gnomad4 EAS exome AF: 0.205

Gnomad4 SAS exome AF: 0.266

Gnomad4 FIN exome AF: 0.354

Gnomad4 NFE exome AF: 0.400

Gnomad4 OTH exome AF: 0.363

GnomAD4 genome AF: 0.357 AC: 54292 AN: 152132 Hom.: 10078 Cov.: 33 AF XY: 0.351 AC XY: 26064 AN XY: 74356

Gnomad4 AFR AF: 0.304

Gnomad4 AMR AF: 0.383

Gnomad4 ASJ AF: 0.418

Gnomad4 EAS AF: 0.187

Gnomad4 SAS AF: 0.243

Gnomad4 FIN AF: 0.343

Gnomad4 NFE AF: 0.402

Gnomad4 OTH AF: 0.362

Alfa AF: 0.391 Hom.: 1642

Bravo AF: 0.360

Asia WGS AF: 0.209 AC: 729 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.77
DANN	Benign	0.37

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: rs2717701; hg19: chr16-3066168;