rs1155884

Variant names:

• chr3-190323165-G-T
• rs1155884
• NM_001378492.1:c.-279+8106G>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.-279+8106G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 151,924 control chromosomes in the GnomAD database, including 20,207 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 0.51 (20207 hom., cov: 32)
• Consequence: CLDN16 NM_001378492.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0810
• Publications: 6 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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLDN16	NM_001378492.1	c.-279+8106G>T		intron_variant	Intron 2 of 8		NP_001365421.1
CLDN16	NM_001378493.1	c.-279+32574G>T		intron_variant	Intron 1 of 7		NP_001365422.1
CLDN16	XM_047447333.1	c.-170+504G>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.121+504G>T		intron_variant	Intron 1 of 4	4

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77751 AN: 151806 Hom.: 20210 Cov.: 32

Gnomad AFR AF: 0.581

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.703

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.498

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

GnomAD4 genome AF: 0.512 AC: 77779 AN: 151924 Hom.: 20207 Cov.: 32 AF XY: 0.510 AC XY: 37851 AN XY: 74224

African (AFR) AF: 0.580 AC: 24029 AN: 41408

American (AMR) AF: 0.500 AC: 7636 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.466 AC: 1618 AN: 3472

East Asian (EAS) AF: 0.702 AC: 3627 AN: 5166

South Asian (SAS) AF: 0.374 AC: 1798 AN: 4806

European-Finnish (FIN) AF: 0.474 AC: 4990 AN: 10532

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.475 AC: 32298 AN: 67956

Other (OTH) AF: 0.497 AC: 1047 AN: 2108

Alfa AF: 0.497 Hom.: 4581

Bravo AF: 0.524

Asia WGS AF: 0.542 AC: 1882 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.1
DANN	Benign	0.71
PhyloP100		-0.081

Splicing

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

Other links and lift over

dbSNP: rs1155884; hg19: chr3-190040954;