chr3-190387662-C-T

Variant names:

• chr3-190387662-C-T
• rs13080849
• NM_001378492.1:c.-93-575C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001378492.1(CLDN16):​c.-93-575C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,112 control chromosomes in the GnomAD database, including 2,317 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.17 (2317 hom., cov: 32)
• Consequence: CLDN16 NM_001378492.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.77
• Publications: 1 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), ClinGen, Orphanet

ENSG00000297357 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 3-190387662-C-T is Benign according to our data. Variant chr3-190387662-C-T is described in ClinVar as Benign. ClinVar VariationId is 1286736.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.196 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.-93-575C>T		intron	N/A	NP_001365421.1	Q9Y5I7
	CLDN16	NM_001378493.1		c.-93-575C>T		intron	N/A	NP_001365422.1	Q9Y5I7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN16	ENST00000880223.1		c.-93-575C>T		intron	N/A	ENSP00000550282.1
	CLDN16	ENST00000880225.1		c.-93-575C>T		intron	N/A	ENSP00000550284.1
	CLDN16	ENST00000880227.1		c.-93-575C>T		intron	N/A	ENSP00000550286.1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25418 AN: 151994 Hom.: 2321 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.0893

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.167 AC: 25408 AN: 152112 Hom.: 2317 Cov.: 32 AF XY: 0.165 AC XY: 12279 AN XY: 74346

African (AFR) AF: 0.122 AC: 5069 AN: 41516

American (AMR) AF: 0.147 AC: 2244 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 609 AN: 3472

East Asian (EAS) AF: 0.146 AC: 754 AN: 5160

South Asian (SAS) AF: 0.0887 AC: 428 AN: 4824

European-Finnish (FIN) AF: 0.190 AC: 2009 AN: 10558

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.199 AC: 13504 AN: 67988

Other (OTH) AF: 0.179 AC: 378 AN: 2114

Alfa AF: 0.187 Hom.: 4545

Bravo AF: 0.166

Asia WGS AF: 0.0800 AC: 281 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.048
DANN	Benign	0.53
PhyloP100		-1.8
PromoterAI		0.0088	Neutral

Splicing

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

Other links and lift over

dbSNP: rs13080849; hg19: chr3-190105451;