rs12629245

Variant names:

• chr3-190299847-T-G
• rs12629245
• NM_001378492.1:c.-446+9256T>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+9256T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,224 control chromosomes in the GnomAD database, including 923 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 0.11 (923 hom., cov: 32)
• Consequence: CLDN16 NM_001378492.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.141
• 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 (AFR) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLDN16	NM_001378492.1	c.-446+9256T>G		intron_variant	Intron 1 of 8		NP_001365421.1
CLDN16	NM_001378493.1	c.-279+9256T>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+9256T>G		intron_variant	Intron 5 of 6

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16292 AN: 152106 Hom.: 921 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0921

Gnomad ASJ AF: 0.0660

Gnomad EAS AF: 0.0797

Gnomad SAS AF: 0.0424

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0961

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.107 AC: 16300 AN: 152224 Hom.: 923 Cov.: 32 AF XY: 0.106 AC XY: 7892 AN XY: 74442

African (AFR) AF: 0.149 AC: 6177 AN: 41516

American (AMR) AF: 0.0923 AC: 1411 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0660 AC: 229 AN: 3468

East Asian (EAS) AF: 0.0793 AC: 411 AN: 5182

South Asian (SAS) AF: 0.0424 AC: 205 AN: 4834

European-Finnish (FIN) AF: 0.100 AC: 1063 AN: 10602

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0961 AC: 6536 AN: 68010

Other (OTH) AF: 0.111 AC: 234 AN: 2114

Alfa AF: 0.112 Hom.: 183

Bravo AF: 0.110

Asia WGS AF: 0.0460 AC: 161 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	1.9
DANN	Benign	0.56
PhyloP100		-0.14

Splicing

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

Other links and lift over

dbSNP: rs12629245; hg19: chr3-190017636;