3-190388282-AGG-AG

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_006580.4(CLDN16):c.-45delG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 1,613,800 control chromosomes in the GnomAD database, including 41,133 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3025 hom., cov: 27)

Exomes 𝑓: 0.22 ( 38108 hom. )

Consequence

CLDN16
NM_006580.4 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.808

Variant links:

Genes affected

CLDN16 (HGNC:2037): (claudin 16) 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 gene, a member of the claudin family, is an integral membrane protein and a component of tight junction strands. It is found primarily in the kidneys, specifically in the thick ascending limb of Henle, where it acts as either an intercellular pore or ion concentration sensor to regulate the paracellular resorption of magnesium ions. Defects in this gene are a cause of primary hypomagnesemia, which is characterized by massive renal magnesium wasting with hypomagnesemia and hypercalciuria, resulting in nephrocalcinosis and renal failure. This gene and the CLDN1 gene are clustered on chromosome 3q28. [provided by RefSeq, Jun 2010]

CLDN16 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 3-190388282-AG-A is Benign according to our data. Variant chr3-190388282-AG-A is described in ClinVar as [Likely_benign]. Clinvar id is 282608.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-190388282-AG-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CLDN16	NM_006580.4 link	c.-45delG	5_prime_UTR_variant	Exon 1 of 5	ENST00000264734.3	NP_006571.2	Q9Y5I7
CLDN16	NM_001378492.1 link	c.-45delG	5_prime_UTR_variant	Exon 5 of 9		NP_001365421.1
CLDN16	NM_001378493.1 link	c.-45delG	5_prime_UTR_variant	Exon 4 of 8		NP_001365422.1
CLDN16	XM_047447333.1 link	c.-45delG	5_prime_UTR_variant	Exon 3 of 7		XP_047303289.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CLDN16	ENST00000264734 link	c.-45delG	5_prime_UTR_variant	Exon 1 of 5	1	NM_006580.4	ENSP00000264734.3	Q9Y5I7
CLDN16	ENST00000456423 link	c.-45delG	5_prime_UTR_variant	Exon 1 of 2	1		ENSP00000414136.2	F6SGM4
CLDN16	ENST00000468220.1 link	n.306+13682delG	intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes

AF:

0.186

AC:

28236

AN:

151936

Hom.:

3026

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0905

Gnomad AMI

AF:

0.183

Gnomad AMR

AF:

0.175

Gnomad ASJ

AF:

0.269

Gnomad EAS

AF:

0.0262

Gnomad SAS

AF:

0.167

Gnomad FIN

AF:

0.256

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.244

Gnomad OTH

AF:

0.212

GnomAD3 exomes

AF:

0.193

AC:

48452

AN:

250984

Hom.:

5424

AF XY:

0.200

AC XY:

27178

AN XY:

135642

show subpopulations

Gnomad AFR exome

AF:

0.0857

Gnomad AMR exome

AF:

0.110

Gnomad ASJ exome

AF:

0.276

Gnomad EAS exome

AF:

0.0199

Gnomad SAS exome

AF:

0.169

Gnomad FIN exome

AF:

0.254

Gnomad NFE exome

AF:

0.248

Gnomad OTH exome

AF:

0.215

GnomAD4 exome

AF:

0.222

AC:

324459

AN:

1461746

Hom.:

38108

Cov.:

AF XY:

0.222

AC XY:

161306

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.0869

Gnomad4 AMR exome

AF:

0.113

Gnomad4 ASJ exome

AF:

0.273

Gnomad4 EAS exome

AF:

0.0291

Gnomad4 SAS exome

AF:

0.172

Gnomad4 FIN exome

AF:

0.253

Gnomad4 NFE exome

AF:

0.239

Gnomad4 OTH exome

AF:

0.216

GnomAD4 genome

AF:

0.186

AC:

28248

AN:

152054

Hom.:

3025

Cov.:

AF XY:

0.186

AC XY:

13792

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.0907

Gnomad4 AMR

AF:

0.174

Gnomad4 ASJ

AF:

0.269

Gnomad4 EAS

AF:

0.0265

Gnomad4 SAS

AF:

0.168

Gnomad4 FIN

AF:

0.256

Gnomad4 NFE

AF:

0.244

Gnomad4 OTH

AF:

0.208

Alfa

AF:

0.226

Hom.:

714

Bravo

AF:

0.172

Asia WGS

AF:

0.0890

AC:

312

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary hypomagnesemia

Benign:3

Jul 20, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 22, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:2

Sep 14, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 10, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

p.Arg56fs in exon 1 of CLDN16: This variant is not expected to have clinical sig nificance because it has been identified in 25% (16723/66656) of European chromo somes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org) . This variant only occurs in cis with c.166G>C to create combined c.165_166del insC variant. Variant has ~19% MAF. Gene uses a downstream start site (Met71) -

not provided

Benign:2

Jan 11, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over