rs6780419

Positions:

• chr3-190338533-C-T

Variant summary

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

The NM_001378492.1(CLDN16):​c.-279+23474C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 151,890 control chromosomes in the GnomAD database, including 11,547 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 0.38 (11547 hom., cov: 32)
• Consequence: CLDN16 NM_001378492.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.651

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLDN16	NM_001378492.1	c.-279+23474C>T		intron_variant			NP_001365421.1
CLDN16	NM_001378493.1	c.-278-32360C>T		intron_variant			NP_001365422.1
CLDN16	XM_047447333.1	c.-170+15872C>T		intron_variant			XP_047303289.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLDN16	ENST00000468220.1	n.121+15872C>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58090 AN: 151772 Hom.: 11537 Cov.: 32

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.685

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.369

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

GnomAD4 genome AF: 0.383 AC: 58129 AN: 151890 Hom.: 11547 Cov.: 32 AF XY: 0.388 AC XY: 28805 AN XY: 74226

Gnomad4 AFR AF: 0.404

Gnomad4 AMR AF: 0.424

Gnomad4 ASJ AF: 0.360

Gnomad4 EAS AF: 0.685

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.409

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.366

Alfa AF: 0.353 Hom.: 17921

Bravo AF: 0.390

Asia WGS AF: 0.475 AC: 1649 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6780419; hg19: chr3-190056322;