rs72466472

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_021101.5(CLDN1):c.108C>T(p.Ala36Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0356 in 1,614,160 control chromosomes in the GnomAD database, including 1,282 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 117 hom., cov: 33)

Exomes 𝑓: 0.036 ( 1165 hom. )

Consequence

CLDN1
NM_021101.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.13

Variant links:

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]

CLDN1 links:

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]

CLDN16 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 3-190322099-G-A is Benign according to our data. Variant chr3-190322099-G-A is described in ClinVar as [Benign]. Clinvar id is 261402.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.13 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLDN1	NM_021101.5 link	c.108C>T	p.Ala36Ala	synonymous_variant	Exon 1 of 4	ENST00000295522.4	NP_066924.1	O95832A5JSJ9
CLDN16	NM_001378492.1 link	c.-279+7040G>A		intron_variant	Intron 2 of 8		NP_001365421.1
CLDN16	NM_001378493.1 link	c.-279+31508G>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 link	c.108C>T	p.Ala36Ala	synonymous_variant	Exon 1 of 4	1	NM_021101.5	ENSP00000295522.3		O95832

Frequencies

GnomAD3 genomes

AF:

0.0311

AC:

4728

AN:

152178

Hom.:

117

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00668

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0476

Gnomad ASJ

AF:

0.0637

Gnomad EAS

AF:

0.0786

Gnomad SAS

AF:

0.0801

Gnomad FIN

AF:

0.0449

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0314

Gnomad OTH

AF:

0.0363

GnomAD3 exomes

AF:

0.0449

AC:

11287

AN:

251404

Hom.:

303

AF XY:

0.0477

AC XY:

6487

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.00578

Gnomad AMR exome

AF:

0.0434

Gnomad ASJ exome

AF:

0.0619

Gnomad EAS exome

AF:

0.0833

Gnomad SAS exome

AF:

0.0822

Gnomad FIN exome

AF:

0.0401

Gnomad NFE exome

AF:

0.0341

Gnomad OTH exome

AF:

0.0442

GnomAD4 exome

AF:

0.0361

AC:

52707

AN:

1461864

Hom.:

1165

Cov.:

AF XY:

0.0375

AC XY:

27299

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.00517

Gnomad4 AMR exome

AF:

0.0445

Gnomad4 ASJ exome

AF:

0.0599

Gnomad4 EAS exome

AF:

0.0759

Gnomad4 SAS exome

AF:

0.0797

Gnomad4 FIN exome

AF:

0.0391

Gnomad4 NFE exome

AF:

0.0308

Gnomad4 OTH exome

AF:

0.0398

GnomAD4 genome

AF:

0.0310

AC:

4727

AN:

152296

Hom.:

117

Cov.:

AF XY:

0.0341

AC XY:

2540

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00666

Gnomad4 AMR

AF:

0.0477

Gnomad4 ASJ

AF:

0.0637

Gnomad4 EAS

AF:

0.0788

Gnomad4 SAS

AF:

0.0797

Gnomad4 FIN

AF:

0.0449

Gnomad4 NFE

AF:

0.0314

Gnomad4 OTH

AF:

0.0350

Alfa

AF:

0.0268

Hom.:

Bravo

AF:

0.0292

Asia WGS

AF:

0.0630

AC:

219

AN:

3478

EpiCase

AF:

0.0321

EpiControl

AF:

0.0372

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

6.1

DANN

Benign

0.95

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over