3-190338371-C-G

Variant names:

• chr3-190338371-C-G
• rs3846100
• NM_001378492.1:c.-279+23312C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378492.1(CLDN16):​c.-279+23312C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.606 in 152,074 control chromosomes in the GnomAD database, including 29,176 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 0.61 (29176 hom., cov: 33)
• Consequence: CLDN16 NM_001378492.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0590
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• renal hypomagnesemia 3

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLDN16	NM_001378492.1	c.-279+23312C>G		intron_variant	Intron 2 of 8		NP_001365421.1
CLDN16	NM_001378493.1	c.-278-32522C>G		intron_variant	Intron 1 of 7		NP_001365422.1
CLDN16	XM_047447333.1	c.-170+15710C>G		intron_variant	Intron 1 of 6		XP_047303289.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLDN16	ENST00000468220.1	n.121+15710C>G		intron_variant	Intron 1 of 4	4

Frequencies

GnomAD3 genomes AF: 0.606 AC: 92117 AN: 151956 Hom.: 29151 Cov.: 33

Gnomad AFR AF: 0.791

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.785

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.531

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.506

Gnomad OTH AF: 0.574

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.606 AC: 92190 AN: 152074 Hom.: 29176 Cov.: 33 AF XY: 0.606 AC XY: 45074 AN XY: 74352

African (AFR) AF: 0.790 AC: 32790 AN: 41492

American (AMR) AF: 0.579 AC: 8841 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.542 AC: 1882 AN: 3472

East Asian (EAS) AF: 0.784 AC: 4069 AN: 5188

South Asian (SAS) AF: 0.548 AC: 2635 AN: 4812

European-Finnish (FIN) AF: 0.531 AC: 5619 AN: 10572

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.506 AC: 34386 AN: 67954

Other (OTH) AF: 0.573 AC: 1210 AN: 2110

Alfa AF: 0.388 Hom.: 889

Bravo AF: 0.622

Asia WGS AF: 0.675 AC: 2347 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.0
DANN	Benign	0.40
PhyloP100		0.059

Splicing

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

Other links and lift over

dbSNP: rs3846100; hg19: chr3-190056160;