chr3-190345831-C-T

Variant names:

• chr3-190345831-C-T
• rs3846102
• NM_001378492.1:c.-278-25062C>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.-278-25062C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 152,048 control chromosomes in the GnomAD database, including 34,834 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 0.66 (34834 hom., cov: 32)
• Consequence: CLDN16 NM_001378492.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.907 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLDN16	NM_001378492.1	c.-278-25062C>T		intron_variant	Intron 2 of 8		NP_001365421.1
CLDN16	NM_001378493.1	c.-278-25062C>T		intron_variant	Intron 1 of 7		NP_001365422.1
CLDN16	XM_047447333.1	c.-170+23170C>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+23170C>T		intron_variant	Intron 1 of 4	4

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100395 AN: 151930 Hom.: 34786 Cov.: 32

Gnomad AFR AF: 0.855

Gnomad AMI AF: 0.640

Gnomad AMR AF: 0.678

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.929

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.645

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

GnomAD4 genome AF: 0.661 AC: 100502 AN: 152048 Hom.: 34834 Cov.: 32 AF XY: 0.663 AC XY: 49244 AN XY: 74320

African (AFR) AF: 0.855 AC: 35482 AN: 41476

American (AMR) AF: 0.678 AC: 10360 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 1940 AN: 3468

East Asian (EAS) AF: 0.929 AC: 4812 AN: 5182

South Asian (SAS) AF: 0.618 AC: 2975 AN: 4814

European-Finnish (FIN) AF: 0.547 AC: 5775 AN: 10552

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.545 AC: 37021 AN: 67974

Other (OTH) AF: 0.647 AC: 1363 AN: 2108

Alfa AF: 0.578 Hom.: 73382

Bravo AF: 0.685

Asia WGS AF: 0.799 AC: 2775 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.22
PhyloP100		-0.045

Splicing

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

Other links and lift over

dbSNP: rs3846102; hg19: chr3-190063620;