rs12696600

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_021101.5(CLDN1):c.-212G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 594,924 control chromosomes in the GnomAD database, including 99,434 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 28339 hom., cov: 34)

Exomes 𝑓: 0.56 ( 71095 hom. )

Consequence

CLDN1
NM_021101.5 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.01

Publications

13 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 3-190322418-C-A is Benign according to our data. Variant chr3-190322418-C-A is described in ClinVar as Benign. ClinVar VariationId is 1259600.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.759 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	Effect	Exon Rank	Protein	UniProt
CLDN1	NM_021101.5	MANE Select	c.-212G>T	5_prime_UTR	Exon 1 of 4	NP_066924.1	O95832
CLDN16	NM_001378492.1		c.-279+7359C>A	intron	N/A	NP_001365421.1	Q9Y5I7
CLDN16	NM_001378493.1		c.-279+31827C>A	intron	N/A	NP_001365422.1	Q9Y5I7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CLDN1	ENST00000295522.4	TSL:1 MANE Select	c.-212G>T	5_prime_UTR	Exon 1 of 4	ENSP00000295522.3	O95832
CLDN16	ENST00000880223.1		c.-522C>A	upstream_gene	N/A	ENSP00000550282.1
CLDN16	ENST00000880225.1		c.-545C>A	upstream_gene	N/A	ENSP00000550284.1

Frequencies

GnomAD3 genomes

AF:

0.602

AC:

91471

AN:

151982

Hom.:

28318

Cov.:

show subpopulations

Gnomad AFR

AF:

0.745

Gnomad AMI

AF:

0.646

Gnomad AMR

AF:

0.573

Gnomad ASJ

AF:

0.551

Gnomad EAS

AF:

0.780

Gnomad SAS

AF:

0.554

Gnomad FIN

AF:

0.540

Gnomad MID

AF:

0.658

Gnomad NFE

AF:

0.524

Gnomad OTH

AF:

0.575

GnomAD4 exome

AF:

0.561

AC:

248224

AN:

442824

Hom.:

71095

Cov.:

AF XY:

0.557

AC XY:

130024

AN XY:

233324

show subpopulations

African (AFR)

AF:

0.738

AC:

9130

AN:

12368

American (AMR)

AF:

0.598

AC:

11448

AN:

19152

Ashkenazi Jewish (ASJ)

AF:

0.564

AC:

7638

AN:

13540

East Asian (EAS)

AF:

0.810

AC:

24855

AN:

30670

South Asian (SAS)

AF:

0.550

AC:

25286

AN:

45936

European-Finnish (FIN)

AF:

0.526

AC:

15085

AN:

28670

Middle Eastern (MID)

AF:

0.565

AC:

1084

AN:

1920

European-Non Finnish (NFE)

AF:

0.525

AC:

139117

AN:

265006

Other (OTH)

AF:

0.570

AC:

14581

AN:

25562

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

5374

10748

16123

21497

26871

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

760

1520

2280

3040

3800

<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:

0.602

AC:

91536

AN:

152100

Hom.:

28339

Cov.:

AF XY:

0.602

AC XY:

44741

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.744

AC:

30922

AN:

41540

American (AMR)

AF:

0.573

AC:

8769

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.551

AC:

1912

AN:

3470

East Asian (EAS)

AF:

0.779

AC:

3995

AN:

5128

South Asian (SAS)

AF:

0.553

AC:

2665

AN:

4822

European-Finnish (FIN)

AF:

0.540

AC:

5709

AN:

10580

Middle Eastern (MID)

AF:

0.663

AC:

195

AN:

294

European-Non Finnish (NFE)

AF:

0.524

AC:

35569

AN:

67944

Other (OTH)

AF:

0.574

AC:

1212

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1880

3759

5639

7518

9398

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

750

1500

2250

3000

3750

<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:

0.564

Hom.:

15134

Bravo

AF:

0.615

Asia WGS

AF:

0.678

AC:

2355

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

6.8

(source)

DANN

Benign

0.81

PhyloP100

-1.0

PromoterAI

-0.081

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

Mutation Taster

=298/2

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