rs72466472

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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

Publications

7 publications found

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 Gene-Disease associations (from GenCC):

renal hypomagnesemia 3
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen

CLDN16 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021101.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLDN1	NM_021101.5	MANE Select	c.108C>T	p.Ala36Ala	synonymous	Exon 1 of 4	NP_066924.1	O95832
CLDN16	NM_001378492.1		c.-279+7040G>A		intron	N/A	NP_001365421.1	Q9Y5I7
CLDN16	NM_001378493.1		c.-279+31508G>A		intron	N/A	NP_001365422.1	Q9Y5I7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN1	ENST00000295522.4	TSL:1 MANE Select	c.108C>T	p.Ala36Ala	synonymous	Exon 1 of 4	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

GnomAD2 exomes

AF:

0.0449

AC:

11287

AN:

251404

AF XY:

0.0477

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 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

African (AFR)

AF:

0.00517

AC:

173

AN:

33480

American (AMR)

AF:

0.0445

AC:

1989

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0599

AC:

1566

AN:

26136

East Asian (EAS)

AF:

0.0759

AC:

3014

AN:

39700

South Asian (SAS)

AF:

0.0797

AC:

6875

AN:

86258

European-Finnish (FIN)

AF:

0.0391

AC:

2090

AN:

53402

Middle Eastern (MID)

AF:

0.0515

AC:

297

AN:

5768

European-Non Finnish (NFE)

AF:

0.0308

AC:

34301

AN:

1112000

Other (OTH)

AF:

0.0398

AC:

2402

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

3163

6327

9490

12654

15817

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1346

2692

4038

5384

6730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0310

AC:

4727

AN:

152296

Hom.:

117

Cov.:

AF XY:

0.0341

AC XY:

2540

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.00666

AC:

277

AN:

41566

American (AMR)

AF:

0.0477

AC:

730

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0637

AC:

221

AN:

3472

East Asian (EAS)

AF:

0.0788

AC:

407

AN:

5164

South Asian (SAS)

AF:

0.0797

AC:

385

AN:

4830

European-Finnish (FIN)

AF:

0.0449

AC:

477

AN:

10620

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0314

AC:

2139

AN:

68020

Other (OTH)

AF:

0.0350

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

229

458

688

917

1146

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0309

Hom.:

157

Bravo

AF:

0.0292

Asia WGS

AF:

0.0630

AC:

219

AN:

3478

EpiCase

AF:

0.0321

EpiControl

AF:

0.0372

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

6.1

(source)

DANN

Benign

0.95

PhyloP100

-2.1

PromoterAI

-0.059

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over