chr3-190312737-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_021101.5(CLDN1):c.388+135C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 931,762 control chromosomes in the GnomAD database, including 29,987 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.26 ( 5415 hom., cov: 33)

Exomes 𝑓: 0.25 ( 24572 hom. )

Consequence

CLDN1
NM_021101.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.232

Publications

4 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 links:

P3H2-AS1 (HGNC:40886): (P3H2 antisense RNA 1)

P3H2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 3-190312737-G-A is Benign according to our data. Variant chr3-190312737-G-A is described in ClinVar as Benign. ClinVar VariationId is 1265460.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.313 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.388+135C>T	intron	N/A	NP_066924.1	O95832
CLDN16	NM_001378492.1		c.-445-2156G>A	intron	N/A	NP_001365421.1	Q9Y5I7
CLDN16	NM_001378493.1		c.-279+22146G>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.388+135C>T	intron	N/A	ENSP00000295522.3	O95832
CLDN1	ENST00000490800.1	TSL:2	n.347+135C>T	intron	N/A
P3H2-AS1	ENST00000747181.1		n.627-2156G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.262

AC:

39800

AN:

151976

Hom.:

5421

Cov.:

show subpopulations

Gnomad AFR

AF:

0.318

Gnomad AMI

AF:

0.364

Gnomad AMR

AF:

0.230

Gnomad ASJ

AF:

0.262

Gnomad EAS

AF:

0.182

Gnomad SAS

AF:

0.265

Gnomad FIN

AF:

0.182

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.251

Gnomad OTH

AF:

0.274

GnomAD4 exome

AF:

0.249

AC:

193752

AN:

779668

Hom.:

24572

AF XY:

0.250

AC XY:

101751

AN XY:

407530

show subpopulations

African (AFR)

AF:

0.313

AC:

6299

AN:

20112

American (AMR)

AF:

0.211

AC:

8043

AN:

38098

Ashkenazi Jewish (ASJ)

AF:

0.249

AC:

4957

AN:

19884

East Asian (EAS)

AF:

0.174

AC:

6230

AN:

35864

South Asian (SAS)

AF:

0.270

AC:

18053

AN:

66844

European-Finnish (FIN)

AF:

0.183

AC:

8375

AN:

45656

Middle Eastern (MID)

AF:

0.330

AC:

1082

AN:

3282

European-Non Finnish (NFE)

AF:

0.256

AC:

131194

AN:

512274

Other (OTH)

AF:

0.253

AC:

9519

AN:

37654

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

7305

14609

21914

29218

36523

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2766

5532

8298

11064

13830

<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:

0.262

AC:

39818

AN:

152094

Hom.:

5415

Cov.:

AF XY:

0.259

AC XY:

19238

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.317

AC:

13172

AN:

41488

American (AMR)

AF:

0.230

AC:

3510

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.262

AC:

906

AN:

3464

East Asian (EAS)

AF:

0.182

AC:

943

AN:

5176

South Asian (SAS)

AF:

0.264

AC:

1274

AN:

4820

European-Finnish (FIN)

AF:

0.182

AC:

1922

AN:

10580

Middle Eastern (MID)

AF:

0.323

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.251

AC:

17087

AN:

67972

Other (OTH)

AF:

0.274

AC:

578

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1501

3002

4502

6003

7504

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

416

832

1248

1664

2080

<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:

0.262

Hom.:

5671

Bravo

AF:

0.267

Asia WGS

AF:

0.232

AC:

805

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.4

(source)

DANN

Benign

0.69

PhyloP100

0.23

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

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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