rs6789788

chr3-190337261-T-Cchr3-190337261-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378492.1(CLDN16):c.-279+22202T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0705 in 152,262 control chromosomes in the GnomAD database, including 564 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 0.070 (564 hom., cov: 32)
• Consequence: CLDN16 NM_001378492.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.326

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]

ACMG classification

Verdict is Benign. Variant got -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 = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLDN16	NM_001378492.1	c.-279+22202T>C		intron_variant
CLDN16	NM_001378493.1	c.-278-33632T>C		intron_variant
CLDN16	XM_047447333.1	c.-170+14600T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLDN16	ENST00000468220.1	n.121+14600T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0703 AC: 10695 AN: 152144 Hom.: 558 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0620

Gnomad ASJ AF: 0.0769

Gnomad EAS AF: 0.0811

Gnomad SAS AF: 0.0824

Gnomad FIN AF: 0.0455

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0326

Gnomad OTH AF: 0.0651

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

GnomAD4 genome AF: 0.0705 AC: 10729 AN: 152262 Hom.: 564 Cov.: 32 AF XY: 0.0718 AC XY: 5342 AN XY: 74450

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.0620

Gnomad4 ASJ AF: 0.0769

Gnomad4 EAS AF: 0.0813

Gnomad4 SAS AF: 0.0821

Gnomad4 FIN AF: 0.0455

Gnomad4 NFE AF: 0.0326

Gnomad4 OTH AF: 0.0635

Alfa AF: 0.0469 Hom.: 67

Bravo AF: 0.0740

Asia WGS AF: 0.0730 AC: 252 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	4.5
Dann	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6789788; hg19: chr3-190055050;