3-190301771-A-G

Variant names:

• chr3-190301771-A-G
• rs13092700
• NM_001378492.1:c.-446+11180A>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.-446+11180A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0466 in 152,264 control chromosomes in the GnomAD database, including 252 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 0.047 (252 hom., cov: 32)
• Consequence: CLDN16 NM_001378492.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.835
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLDN16	NM_001378492.1	c.-446+11180A>G		intron_variant	Intron 1 of 8		NP_001365421.1
CLDN16	NM_001378493.1	c.-279+11180A>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.626+11180A>G		intron_variant	Intron 5 of 6

Frequencies

GnomAD3 genomes AF: 0.0467 AC: 7105 AN: 152146 Hom.: 252 Cov.: 32

Gnomad AFR AF: 0.0126

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.0266

Gnomad ASJ AF: 0.0366

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00973

Gnomad FIN AF: 0.0961

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0688

Gnomad OTH AF: 0.0411

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

GnomAD4 genome AF: 0.0466 AC: 7102 AN: 152264 Hom.: 252 Cov.: 32 AF XY: 0.0473 AC XY: 3520 AN XY: 74448

African (AFR) AF: 0.0126 AC: 522 AN: 41580

American (AMR) AF: 0.0264 AC: 404 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0366 AC: 127 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.00995 AC: 48 AN: 4824

European-Finnish (FIN) AF: 0.0961 AC: 1018 AN: 10594

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0688 AC: 4675 AN: 67998

Other (OTH) AF: 0.0406 AC: 86 AN: 2116

Alfa AF: 0.0427 Hom.: 118

Bravo AF: 0.0414

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.73
DANN	Benign	0.36
PhyloP100		-0.83

Splicing

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

Other links and lift over

dbSNP: rs13092700; hg19: chr3-190019560;