rs3732923

Variant names:

• chr3-190316920-T-A
• rs3732923
• NM_021101.5:c.224-3884A>T

Your query was ambiguous. Multiple possible variants found:

• chr3-190316920-T-A
• chr3-190316920-T-C

Variant summary

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

The NM_021101.5(CLDN1):​c.224-3884A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 152,034 control chromosomes in the GnomAD database, including 15,951 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 0.45 (15951 hom., cov: 32)
• Consequence: CLDN1 NM_021101.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.64
• Publications: 6 publications found

Genes affected

CLDN1 (HGNC:2032): (claudin 1) 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. Loss of function mutations result in neonatal ichthyosis-sclerosing cholangitis syndrome. [provided by RefSeq, Jul 2008]

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.775 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLDN1	NM_021101.5	c.224-3884A>T		intron_variant	Intron 1 of 3	ENST00000295522.4	NP_066924.1
CLDN16	NM_001378492.1	c.-279+1861T>A		intron_variant	Intron 2 of 8		NP_001365421.1
CLDN16	NM_001378493.1	c.-279+26329T>A		intron_variant	Intron 1 of 7		NP_001365422.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLDN1	ENST00000295522.4	c.224-3884A>T		intron_variant	Intron 1 of 3	1	NM_021101.5	ENSP00000295522.3
P3H2-AS1	ENST00000747181.1	n.793+1861T>A		intron_variant	Intron 6 of 6

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68289 AN: 151916 Hom.: 15938 Cov.: 32

Gnomad AFR AF: 0.504

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.795

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.434

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

GnomAD4 genome AF: 0.450 AC: 68342 AN: 152034 Hom.: 15951 Cov.: 32 AF XY: 0.455 AC XY: 33805 AN XY: 74316

African (AFR) AF: 0.503 AC: 20880 AN: 41472

American (AMR) AF: 0.487 AC: 7427 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 1338 AN: 3470

East Asian (EAS) AF: 0.795 AC: 4119 AN: 5178

South Asian (SAS) AF: 0.460 AC: 2217 AN: 4816

European-Finnish (FIN) AF: 0.427 AC: 4506 AN: 10560

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.389 AC: 26403 AN: 67960

Other (OTH) AF: 0.436 AC: 920 AN: 2112

Alfa AF: 0.247 Hom.: 547

Bravo AF: 0.460

Asia WGS AF: 0.624 AC: 2159 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.4
DANN	Benign	0.64
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs3732923; hg19: chr3-190034709;