3-190347883-A-G

Variant names:

• chr3-190347883-A-G
• rs12696601
• NM_001378492.1:c.-278-23010A>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.-278-23010A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 151,720 control chromosomes in the GnomAD database, including 7,475 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 0.30 (7475 hom., cov: 30)
• Consequence: CLDN16 NM_001378492.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.584 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN16	NM_001378492.1		c.-278-23010A>G		intron	N/A	NP_001365421.1
	CLDN16	NM_001378493.1		c.-278-23010A>G		intron	N/A	NP_001365422.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN16	ENST00000468220.1	TSL:4	n.122-23010A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.303 AC: 45980 AN: 151602 Hom.: 7477 Cov.: 30

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.602

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.290

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.302

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

GnomAD4 genome AF: 0.303 AC: 45981 AN: 151720 Hom.: 7475 Cov.: 30 AF XY: 0.308 AC XY: 22818 AN XY: 74136

African (AFR) AF: 0.228 AC: 9430 AN: 41386

American (AMR) AF: 0.360 AC: 5476 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 983 AN: 3472

East Asian (EAS) AF: 0.602 AC: 3076 AN: 5112

South Asian (SAS) AF: 0.223 AC: 1071 AN: 4806

European-Finnish (FIN) AF: 0.381 AC: 3996 AN: 10500

Middle Eastern (MID) AF: 0.291 AC: 85 AN: 292

European-Non Finnish (NFE) AF: 0.307 AC: 20821 AN: 67912

Other (OTH) AF: 0.301 AC: 634 AN: 2108

Alfa AF: 0.300 Hom.: 11837

Bravo AF: 0.305

Asia WGS AF: 0.398 AC: 1383 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.3
DANN	Benign	0.63
PhyloP100		1.2

Splicing

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

Other links and lift over

dbSNP: rs12696601; hg19: chr3-190065672;