rs2717701

Variant names:

• chr16-3016167-G-C
• rs2717701
• NM_021195.5:c.-21-125C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021195.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN6	NM_021195.5	MANE Select	c.-21-125C>G		intron	N/A	NP_067018.2	P56747

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN6	ENST00000328796.5	TSL:1 MANE Select	c.-21-125C>G		intron	N/A	ENSP00000328674.4	P56747
	CLDN6	ENST00000396925.1	TSL:5	c.-21-125C>G		intron	N/A	ENSP00000380131.1	P56747
	CLDN6	ENST00000939715.1		c.-16-130C>G		intron	N/A	ENSP00000609774.1

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

African (AFR) AF: 0.304 AC: 4973 AN: 16338

American (AMR) AF: 0.385 AC: 7527 AN: 19554

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 6290 AN: 15084

East Asian (EAS) AF: 0.205 AC: 6557 AN: 31956

South Asian (SAS) AF: 0.266 AC: 13338 AN: 50094

European-Finnish (FIN) AF: 0.354 AC: 11954 AN: 33732

Middle Eastern (MID) AF: 0.397 AC: 1100 AN: 2768

European-Non Finnish (NFE) AF: 0.400 AC: 183887 AN: 459352

Other (OTH) AF: 0.363 AC: 11921 AN: 32852

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

African (AFR) AF: 0.304 AC: 12630 AN: 41486

American (AMR) AF: 0.383 AC: 5852 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.418 AC: 1449 AN: 3468

East Asian (EAS) AF: 0.187 AC: 970 AN: 5176

South Asian (SAS) AF: 0.243 AC: 1176 AN: 4830

European-Finnish (FIN) AF: 0.343 AC: 3633 AN: 10586

Middle Eastern (MID) AF: 0.414 AC: 121 AN: 292

European-Non Finnish (NFE) AF: 0.402 AC: 27293 AN: 67970

Other (OTH) AF: 0.362 AC: 766 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.77
DANN	Benign	0.37
PhyloP100		-0.81
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2717701; hg19: chr16-3066168;