rs9290930

Variant names:

• chr3-190356900-C-T
• rs9290930
• NM_001378492.1:c.-278-13993C>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.-278-13993C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 151,598 control chromosomes in the GnomAD database, including 12,820 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 0.40 (12820 hom., cov: 32)
• Consequence: CLDN16 NM_001378492.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.731
• Publications: 2 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLDN16	NM_001378492.1	c.-278-13993C>T		intron_variant	Intron 2 of 8		NP_001365421.1
CLDN16	NM_001378493.1	c.-278-13993C>T		intron_variant	Intron 1 of 7		NP_001365422.1
CLDN16	XM_047447333.1	c.-169-17628C>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.122-13993C>T		intron_variant	Intron 1 of 4	4

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60047 AN: 151480 Hom.: 12820 Cov.: 32

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.421

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

GnomAD4 genome AF: 0.396 AC: 60087 AN: 151598 Hom.: 12820 Cov.: 32 AF XY: 0.392 AC XY: 29020 AN XY: 74050

African (AFR) AF: 0.260 AC: 10779 AN: 41422

American (AMR) AF: 0.366 AC: 5567 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 1652 AN: 3464

East Asian (EAS) AF: 0.156 AC: 799 AN: 5128

South Asian (SAS) AF: 0.361 AC: 1736 AN: 4806

European-Finnish (FIN) AF: 0.442 AC: 4646 AN: 10512

Middle Eastern (MID) AF: 0.538 AC: 157 AN: 292

European-Non Finnish (NFE) AF: 0.494 AC: 33449 AN: 67758

Other (OTH) AF: 0.416 AC: 875 AN: 2104

Alfa AF: 0.473 Hom.: 19940

Bravo AF: 0.384

Asia WGS AF: 0.244 AC: 850 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.0
DANN	Benign	0.62
PhyloP100		0.73

Splicing

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

Other links and lift over

dbSNP: rs9290930; hg19: chr3-190074689;