chr3-190387530-G-A

Position:

• chr3-190387530-G-A

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.-93-707G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,144 control chromosomes in the GnomAD database, including 3,084 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.19 (3084 hom., cov: 33)
• Consequence: CLDN16 NM_001378492.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.52

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=-0.9).
• BP6: Variant 3-190387530-G-A is Benign according to our data. Variant chr3-190387530-G-A is described in ClinVar as [Benign]. Clinvar id is 1229364.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLDN16	NM_001378492.1	c.-93-707G>A		intron_variant			NP_001365421.1
CLDN16	NM_001378493.1	c.-93-707G>A		intron_variant			NP_001365422.1
CLDN16	XM_047447333.1	c.-93-707G>A		intron_variant			XP_047303289.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLDN16	ENST00000468220.1	n.306+12927G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28350 AN: 152026 Hom.: 3085 Cov.: 33

Gnomad AFR AF: 0.0905

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.0262

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.212

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

GnomAD4 genome AF: 0.186 AC: 28362 AN: 152144 Hom.: 3084 Cov.: 33 AF XY: 0.186 AC XY: 13869 AN XY: 74376

Gnomad4 AFR AF: 0.0906

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.0265

Gnomad4 SAS AF: 0.168

Gnomad4 FIN AF: 0.259

Gnomad4 NFE AF: 0.244

Gnomad4 OTH AF: 0.208

Alfa AF: 0.213 Hom.: 443

Bravo AF: 0.172

Asia WGS AF: 0.0890 AC: 312 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	-0.90
CADD	Benign	0.10
DANN	Benign	0.38

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs62278698; hg19: chr3-190105319;