rs9809713

Positions:

• chr3-190329263-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378492.1(CLDN16):​c.-279+14204T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 151,916 control chromosomes in the GnomAD database, including 18,883 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 0.50 (18883 hom., cov: 31)
• Consequence: CLDN16 NM_001378492.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.192

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLDN16	NM_001378492.1	c.-279+14204T>C		intron_variant
CLDN16	NM_001378493.1	c.-279+38672T>C		intron_variant
CLDN16	XM_047447333.1	c.-170+6602T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLDN16	ENST00000468220.1	n.121+6602T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.495 AC: 75190 AN: 151798 Hom.: 18886 Cov.: 31

Gnomad AFR AF: 0.531

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.702

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.484

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

GnomAD4 genome AF: 0.495 AC: 75222 AN: 151916 Hom.: 18883 Cov.: 31 AF XY: 0.494 AC XY: 36689 AN XY: 74242

Gnomad4 AFR AF: 0.530

Gnomad4 AMR AF: 0.499

Gnomad4 ASJ AF: 0.459

Gnomad4 EAS AF: 0.701

Gnomad4 SAS AF: 0.375

Gnomad4 FIN AF: 0.472

Gnomad4 NFE AF: 0.470

Gnomad4 OTH AF: 0.483

Alfa AF: 0.489 Hom.: 2293

Bravo AF: 0.506

Asia WGS AF: 0.546 AC: 1896 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.78
DANN	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9809713; hg19: chr3-190047052;