chr3-190387662-C-T

Position:

• chr3-190387662-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001378492.1(CLDN16):​c.-93-575C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,112 control chromosomes in the GnomAD database, including 2,317 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.17 (2317 hom., cov: 32)
• Consequence: CLDN16 NM_001378492.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.77

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 3-190387662-C-T is Benign according to our data. Variant chr3-190387662-C-T is described in ClinVar as [Benign]. Clinvar id is 1286736.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLDN16	NM_001378492.1	c.-93-575C>T		intron_variant			NP_001365421.1
CLDN16	NM_001378493.1	c.-93-575C>T		intron_variant			NP_001365422.1
CLDN16	XM_047447333.1	c.-93-575C>T		intron_variant			XP_047303289.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLDN16	ENST00000468220.1	n.306+13059C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25418 AN: 151994 Hom.: 2321 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.0893

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.167 AC: 25408 AN: 152112 Hom.: 2317 Cov.: 32 AF XY: 0.165 AC XY: 12279 AN XY: 74346

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.146

Gnomad4 SAS AF: 0.0887

Gnomad4 FIN AF: 0.190

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.179

Alfa AF: 0.189 Hom.: 3659

Bravo AF: 0.166

Asia WGS AF: 0.0800 AC: 281 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 20, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.048
DANN	Benign	0.53

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13080849; hg19: chr3-190105451;