chr3-190322608-C-T

Position:

• chr3-190322608-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The XM_047447333.1(CLDN16):​c.-223C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 292,708 control chromosomes in the GnomAD database, including 36,197 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (20136 hom., cov: 33)
  • Exomes 𝑓: 0.47 (16061 hom.)
• Consequence: CLDN16 XM_047447333.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.94

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 3-190322608-C-T is Benign according to our data. Variant chr3-190322608-C-T is described in ClinVar as [Benign]. Clinvar id is 1242004.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLDN16	XM_047447333.1	c.-223C>T		5_prime_UTR_variant	1/7		XP_047303289.1
CLDN16	NM_001378492.1	c.-279+7549C>T		intron_variant			NP_001365421.1
CLDN16	NM_001378493.1	c.-279+32017C>T		intron_variant			NP_001365422.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLDN16	ENST00000468220.1	n.68C>T		non_coding_transcript_exon_variant	1/5	4

Frequencies

GnomAD3 genomes AF: 0.511 AC: 77626 AN: 151892 Hom.: 20138 Cov.: 33

Gnomad AFR AF: 0.581

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.696

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.497

GnomAD4 exome AF: 0.470 AC: 66086 AN: 140698 Hom.: 16061 Cov.: 0 AF XY: 0.458 AC XY: 34334 AN XY: 74988

Gnomad4 AFR exome AF: 0.574

Gnomad4 AMR exome AF: 0.549

Gnomad4 ASJ exome AF: 0.482

Gnomad4 EAS exome AF: 0.729

Gnomad4 SAS exome AF: 0.371

Gnomad4 FIN exome AF: 0.468

Gnomad4 NFE exome AF: 0.476

Gnomad4 OTH exome AF: 0.481

GnomAD4 genome AF: 0.511 AC: 77653 AN: 152010 Hom.: 20136 Cov.: 33 AF XY: 0.508 AC XY: 37780 AN XY: 74302

Gnomad4 AFR AF: 0.581

Gnomad4 AMR AF: 0.498

Gnomad4 ASJ AF: 0.466

Gnomad4 EAS AF: 0.695

Gnomad4 SAS AF: 0.372

Gnomad4 FIN AF: 0.471

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.496

Alfa AF: 0.501 Hom.: 2426

Bravo AF: 0.523

Asia WGS AF: 0.540 AC: 1875 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	1.8
DANN	Benign	0.87

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17501976; hg19: chr3-190040397;