3-190337243-C-G

Variant names:

• chr3-190337243-C-G
• rs6776618
• NM_001378492.1:c.-279+22184C>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+22184C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.672 in 152,116 control chromosomes in the GnomAD database, including 35,835 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 0.67 (35835 hom., cov: 33)
• Consequence: CLDN16 NM_001378492.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59
• Publications: 4 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: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.907 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378492.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN16	NM_001378492.1		c.-279+22184C>G		intron	N/A	NP_001365421.1	Q9Y5I7
	CLDN16	NM_001378493.1		c.-278-33650C>G		intron	N/A	NP_001365422.1	Q9Y5I7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN16	ENST00000880223.1		c.-279+14582C>G		intron	N/A	ENSP00000550282.1
	CLDN16	ENST00000880225.1		c.-302+14582C>G		intron	N/A	ENSP00000550284.1
	CLDN16	ENST00000880227.1		c.-94+14582C>G		intron	N/A	ENSP00000550286.1

Frequencies

GnomAD3 genomes AF: 0.671 AC: 102042 AN: 151998 Hom.: 35787 Cov.: 33

Gnomad AFR AF: 0.862

Gnomad AMI AF: 0.640

Gnomad AMR AF: 0.689

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.929

Gnomad SAS AF: 0.644

Gnomad FIN AF: 0.555

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.654

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

GnomAD4 genome AF: 0.672 AC: 102147 AN: 152116 Hom.: 35835 Cov.: 33 AF XY: 0.673 AC XY: 50039 AN XY: 74356

African (AFR) AF: 0.862 AC: 35798 AN: 41528

American (AMR) AF: 0.690 AC: 10545 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 1980 AN: 3466

East Asian (EAS) AF: 0.929 AC: 4812 AN: 5180

South Asian (SAS) AF: 0.644 AC: 3103 AN: 4820

European-Finnish (FIN) AF: 0.555 AC: 5855 AN: 10556

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.558 AC: 37893 AN: 67962

Other (OTH) AF: 0.656 AC: 1385 AN: 2112

Alfa AF: 0.452 Hom.: 1093

Bravo AF: 0.695

Asia WGS AF: 0.805 AC: 2798 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.44
DANN	Benign	0.65
PhyloP100		-1.6

Splicing

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

Other links and lift over

dbSNP: rs6776618; hg19: chr3-190055032;