chr3-190304695-T-G

Variant names:

• chr3-190304695-T-G
• rs9290926
• NM_001378492.1:c.-445-10198T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378492.1(CLDN16):​c.-445-10198T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,044 control chromosomes in the GnomAD database, including 1,682 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 0.12 (1682 hom., cov: 32)
• Consequence: CLDN16 NM_001378492.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.492
• Publications: 1 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]

P3H2-AS1 (HGNC:40886): (P3H2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLDN16	NM_001378492.1	c.-445-10198T>G		intron_variant	Intron 1 of 8		NP_001365421.1
CLDN16	NM_001378493.1	c.-279+14104T>G		intron_variant	Intron 1 of 7		NP_001365422.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P3H2-AS1	ENST00000747181.1	n.627-10198T>G		intron_variant	Intron 5 of 6

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18612 AN: 151926 Hom.: 1686 Cov.: 32

Gnomad AFR AF: 0.0550

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.0435

Gnomad EAS AF: 0.500

Gnomad SAS AF: 0.0987

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.122 AC: 18611 AN: 152044 Hom.: 1682 Cov.: 32 AF XY: 0.126 AC XY: 9333 AN XY: 74294

African (AFR) AF: 0.0549 AC: 2278 AN: 41492

American (AMR) AF: 0.125 AC: 1906 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.0435 AC: 151 AN: 3470

East Asian (EAS) AF: 0.500 AC: 2577 AN: 5154

South Asian (SAS) AF: 0.0981 AC: 473 AN: 4820

European-Finnish (FIN) AF: 0.179 AC: 1891 AN: 10562

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8909 AN: 67976

Other (OTH) AF: 0.104 AC: 220 AN: 2108

Alfa AF: 0.122 Hom.: 162

Bravo AF: 0.118

Asia WGS AF: 0.245 AC: 849 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.6
DANN	Benign	0.60
PhyloP100		0.49

Splicing

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

Other links and lift over

dbSNP: rs9290926; hg19: chr3-190022484;