rs7632915

Positions:

• chr3-190303659-A-C
• chr3-190303659-A-G
• chr3-190303659-A-T

Variant summary

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

The NM_001378492.1(CLDN16):​c.-445-11234A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 152,056 control chromosomes in the GnomAD database, including 31,453 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 0.64 (31453 hom., cov: 32)
• Consequence: CLDN16 NM_001378492.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42

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]

(HGNC:):

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 = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLDN16	NM_001378492.1	c.-445-11234A>C		intron_variant			NP_001365421.1
CLDN16	NM_001378493.1	c.-279+13068A>C		intron_variant			NP_001365422.1
		n.190303659A>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.636 AC: 96648 AN: 151938 Hom.: 31407 Cov.: 32

Gnomad AFR AF: 0.761

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.748

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.581

Gnomad MID AF: 0.586

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.628

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

GnomAD4 genome AF: 0.636 AC: 96740 AN: 152056 Hom.: 31453 Cov.: 32 AF XY: 0.632 AC XY: 46992 AN XY: 74330

Gnomad4 AFR AF: 0.762

Gnomad4 AMR AF: 0.609

Gnomad4 ASJ AF: 0.502

Gnomad4 EAS AF: 0.749

Gnomad4 SAS AF: 0.426

Gnomad4 FIN AF: 0.581

Gnomad4 NFE AF: 0.588

Gnomad4 OTH AF: 0.625

Alfa AF: 0.592 Hom.: 42796

Bravo AF: 0.648

Asia WGS AF: 0.547 AC: 1900 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	11
DANN	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7632915; hg19: chr3-190021448;