rs13340153

Variant names:

• chr3-190353030-C-T
• rs13340153
• NM_001378492.1:c.-278-17863C>T

Variant summary

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

The NM_001378492.1(CLDN16):​c.-278-17863C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 151,964 control chromosomes in the GnomAD database, including 1,146 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 0.10 (1146 hom., cov: 32)
• Consequence: CLDN16 NM_001378492.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLDN16	NM_001378492.1	c.-278-17863C>T		intron_variant	Intron 2 of 8		NP_001365421.1
CLDN16	NM_001378493.1	c.-278-17863C>T		intron_variant	Intron 1 of 7		NP_001365422.1
CLDN16	XM_047447333.1	c.-169-21498C>T		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.122-17863C>T		intron_variant	Intron 1 of 4	4

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15880 AN: 151846 Hom.: 1144 Cov.: 32

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.0264

Gnomad AMR AF: 0.0810

Gnomad ASJ AF: 0.0386

Gnomad EAS AF: 0.0152

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.0889

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0637

Gnomad OTH AF: 0.0866

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

GnomAD4 genome AF: 0.105 AC: 15902 AN: 151964 Hom.: 1146 Cov.: 32 AF XY: 0.104 AC XY: 7717 AN XY: 74254

African (AFR) AF: 0.204 AC: 8458 AN: 41484

American (AMR) AF: 0.0808 AC: 1230 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.0386 AC: 134 AN: 3468

East Asian (EAS) AF: 0.0151 AC: 78 AN: 5174

South Asian (SAS) AF: 0.105 AC: 507 AN: 4808

European-Finnish (FIN) AF: 0.0889 AC: 938 AN: 10554

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0637 AC: 4329 AN: 67936

Other (OTH) AF: 0.0885 AC: 187 AN: 2112

Alfa AF: 0.0778 Hom.: 1045

Bravo AF: 0.107

Asia WGS AF: 0.0890 AC: 307 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.74
DANN	Benign	0.45
PhyloP100		-1.5

Splicing

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

Other links and lift over

dbSNP: rs13340153; hg19: chr3-190070819;