rs1554555

Variant names:

• chr3-190333423-G-A
• rs1554555
• NM_001378492.1:c.-279+18364G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-190333423-G-A
• chr3-190333423-G-C

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+18364G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 151,988 control chromosomes in the GnomAD database, including 34,502 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 0.66 (34502 hom., cov: 32)
• Consequence: CLDN16 NM_001378492.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.430
• 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: 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.907 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLDN16	NM_001378492.1	c.-279+18364G>A		intron_variant	Intron 2 of 8		NP_001365421.1
CLDN16	NM_001378493.1	c.-278-37470G>A		intron_variant	Intron 1 of 7		NP_001365422.1
CLDN16	XM_047447333.1	c.-170+10762G>A		intron_variant	Intron 1 of 6		XP_047303289.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLDN16	ENST00000468220.1	n.121+10762G>A		intron_variant	Intron 1 of 4	4

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100410 AN: 151870 Hom.: 34468 Cov.: 32

Gnomad AFR AF: 0.827

Gnomad AMI AF: 0.638

Gnomad AMR AF: 0.686

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: 0.557

Gnomad OTH AF: 0.647

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

GnomAD4 genome AF: 0.661 AC: 100501 AN: 151988 Hom.: 34502 Cov.: 32 AF XY: 0.662 AC XY: 49218 AN XY: 74292

African (AFR) AF: 0.826 AC: 34286 AN: 41494

American (AMR) AF: 0.687 AC: 10483 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 1978 AN: 3464

East Asian (EAS) AF: 0.929 AC: 4808 AN: 5174

South Asian (SAS) AF: 0.643 AC: 3104 AN: 4824

European-Finnish (FIN) AF: 0.555 AC: 5858 AN: 10548

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

European-Non Finnish (NFE) AF: 0.557 AC: 37837 AN: 67896

Other (OTH) AF: 0.649 AC: 1371 AN: 2112

Alfa AF: 0.632 Hom.: 4919

Bravo AF: 0.683

Asia WGS AF: 0.803 AC: 2778 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.48
DANN	Benign	0.22
PhyloP100		-0.43

Splicing

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

Other links and lift over

dbSNP: rs1554555; hg19: chr3-190051212;