rs6781278

Variant names:

• chr3-190326228-A-G
• rs6781278
• NM_001378492.1:c.-279+11169A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-190326228-A-G
• chr3-190326228-A-T

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+11169A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 151,980 control chromosomes in the GnomAD database, including 27,988 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 0.60 (27988 hom., cov: 32)
• Consequence: CLDN16 NM_001378492.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63
• Publications: 5 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLDN16	NM_001378492.1	c.-279+11169A>G		intron_variant	Intron 2 of 8		NP_001365421.1
CLDN16	NM_001378493.1	c.-279+35637A>G		intron_variant	Intron 1 of 7		NP_001365422.1
CLDN16	XM_047447333.1	c.-170+3567A>G		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+3567A>G		intron_variant	Intron 1 of 4	4

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90625 AN: 151862 Hom.: 27974 Cov.: 32

Gnomad AFR AF: 0.752

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.574

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.785

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.565

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

GnomAD4 genome AF: 0.597 AC: 90689 AN: 151980 Hom.: 27988 Cov.: 32 AF XY: 0.597 AC XY: 44354 AN XY: 74252

African (AFR) AF: 0.751 AC: 31153 AN: 41460

American (AMR) AF: 0.574 AC: 8760 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 1834 AN: 3464

East Asian (EAS) AF: 0.784 AC: 4044 AN: 5156

South Asian (SAS) AF: 0.547 AC: 2635 AN: 4818

European-Finnish (FIN) AF: 0.533 AC: 5629 AN: 10558

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.510 AC: 34685 AN: 67954

Other (OTH) AF: 0.565 AC: 1190 AN: 2108

Alfa AF: 0.542 Hom.: 101496

Bravo AF: 0.611

Asia WGS AF: 0.674 AC: 2342 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.17
DANN	Benign	0.42
PhyloP100		-1.6

Splicing

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

Other links and lift over

dbSNP: rs6781278; hg19: chr3-190044017;