rs10212165

Variant names:

• chr3-190327621-A-G
• rs10212165
• NM_001378492.1:c.-279+12562A>G

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+12562A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,162 control chromosomes in the GnomAD database, including 2,910 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 0.19 (2910 hom., cov: 32)
• Consequence: CLDN16 NM_001378492.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.277
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLDN16	NM_001378492.1	c.-279+12562A>G		intron_variant	Intron 2 of 8		NP_001365421.1
CLDN16	NM_001378493.1	c.-279+37030A>G		intron_variant	Intron 1 of 7		NP_001365422.1
CLDN16	XM_047447333.1	c.-170+4960A>G		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+4960A>G		intron_variant	Intron 1 of 4	4

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28299 AN: 152042 Hom.: 2911 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.186 AC: 28327 AN: 152162 Hom.: 2910 Cov.: 32 AF XY: 0.182 AC XY: 13515 AN XY: 74386

African (AFR) AF: 0.267 AC: 11078 AN: 41492

American (AMR) AF: 0.182 AC: 2791 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 625 AN: 3466

East Asian (EAS) AF: 0.101 AC: 521 AN: 5174

South Asian (SAS) AF: 0.152 AC: 733 AN: 4816

European-Finnish (FIN) AF: 0.110 AC: 1169 AN: 10590

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10772 AN: 68008

Other (OTH) AF: 0.192 AC: 404 AN: 2108

Alfa AF: 0.185 Hom.: 643

Bravo AF: 0.197

Asia WGS AF: 0.149 AC: 519 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	2.8
DANN	Benign	0.39
PhyloP100		0.28

Splicing

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

Other links and lift over

dbSNP: rs10212165; hg19: chr3-190045410;