rs9809713

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001378492.1(CLDN16):​c.-279+14204T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 151,916 control chromosomes in the GnomAD database, including 18,883 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 0.50 ( 18883 hom., cov: 31)

Consequence

CLDN16
NM_001378492.1 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.192
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CLDN16NM_001378492.1 linkuse as main transcriptc.-279+14204T>C intron_variant
CLDN16NM_001378493.1 linkuse as main transcriptc.-279+38672T>C intron_variant
CLDN16XM_047447333.1 linkuse as main transcriptc.-170+6602T>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CLDN16ENST00000468220.1 linkuse as main transcriptn.121+6602T>C intron_variant, non_coding_transcript_variant 4

Frequencies

GnomAD3 genomes
AF:
0.495
AC:
75190
AN:
151798
Hom.:
18886
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.531
Gnomad AMI
AF:
0.622
Gnomad AMR
AF:
0.498
Gnomad ASJ
AF:
0.459
Gnomad EAS
AF:
0.702
Gnomad SAS
AF:
0.376
Gnomad FIN
AF:
0.472
Gnomad MID
AF:
0.576
Gnomad NFE
AF:
0.470
Gnomad OTH
AF:
0.484
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.495
AC:
75222
AN:
151916
Hom.:
18883
Cov.:
31
AF XY:
0.494
AC XY:
36689
AN XY:
74242
show subpopulations
Gnomad4 AFR
AF:
0.530
Gnomad4 AMR
AF:
0.499
Gnomad4 ASJ
AF:
0.459
Gnomad4 EAS
AF:
0.701
Gnomad4 SAS
AF:
0.375
Gnomad4 FIN
AF:
0.472
Gnomad4 NFE
AF:
0.470
Gnomad4 OTH
AF:
0.483
Alfa
AF:
0.489
Hom.:
2293
Bravo
AF:
0.506
Asia WGS
AF:
0.546
AC:
1896
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
0.78
DANN
Benign
0.44

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs9809713; hg19: chr3-190047052; API