NM_001378492.1:c.-278-19806C>T

Variant names:

• chr3-190351087-C-T
• rs11922773
• NM_001378492.1:c.-278-19806C>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.-278-19806C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0508 in 151,826 control chromosomes in the GnomAD database, including 289 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 0.051 (289 hom., cov: 31)
• Consequence: CLDN16 NM_001378492.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.816
• Publications: 1 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0988 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLDN16	NM_001378492.1	c.-278-19806C>T		intron_variant	Intron 2 of 8		NP_001365421.1
CLDN16	NM_001378493.1	c.-278-19806C>T		intron_variant	Intron 1 of 7		NP_001365422.1
CLDN16	XM_047447333.1	c.-169-23441C>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.122-19806C>T		intron_variant	Intron 1 of 4	4

Frequencies

GnomAD3 genomes AF: 0.0508 AC: 7704 AN: 151710 Hom.: 288 Cov.: 31

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0467

Gnomad ASJ AF: 0.0459

Gnomad EAS AF: 0.0588

Gnomad SAS AF: 0.00667

Gnomad FIN AF: 0.0444

Gnomad MID AF: 0.0350

Gnomad NFE AF: 0.0256

Gnomad OTH AF: 0.0465

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

GnomAD4 genome AF: 0.0508 AC: 7718 AN: 151826 Hom.: 289 Cov.: 31 AF XY: 0.0515 AC XY: 3819 AN XY: 74158

African (AFR) AF: 0.101 AC: 4195 AN: 41400

American (AMR) AF: 0.0467 AC: 712 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.0459 AC: 159 AN: 3464

East Asian (EAS) AF: 0.0590 AC: 302 AN: 5122

South Asian (SAS) AF: 0.00688 AC: 33 AN: 4796

European-Finnish (FIN) AF: 0.0444 AC: 469 AN: 10560

Middle Eastern (MID) AF: 0.0379 AC: 11 AN: 290

European-Non Finnish (NFE) AF: 0.0256 AC: 1741 AN: 67944

Other (OTH) AF: 0.0455 AC: 96 AN: 2108

Alfa AF: 0.0104 Hom.: 5

Bravo AF: 0.0539

Asia WGS AF: 0.0300 AC: 105 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.6
DANN	Benign	0.38
PhyloP100		-0.82

Splicing

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

Other links and lift over

dbSNP: rs11922773; hg19: chr3-190068876;