rs55641411

Variant names:

Variant summary

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

The ENST00000468220.1(CLDN16):n.110C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 250,592 control chromosomes in the GnomAD database, including 1,634 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1018 hom., cov: 32)

Exomes 𝑓: 0.096 ( 616 hom. )

Consequence

CLDN16
ENST00000468220.1 non_coding_transcript_exon

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.887

Publications

1 publications found

Variant links:

Genes affected

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:

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 Gene-Disease associations (from GenCC):

neonatal ichthyosis-sclerosing cholangitis syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia, Genomics England PanelApp, G2P

CLDN1 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=-0.72).

BP6

Variant 3-190322650-C-A is Benign according to our data. Variant chr3-190322650-C-A is described in ClinVar as Benign. ClinVar VariationId is 1266716.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CLDN16	XM_047447333.1 link	c.-181C>A	5_prime_UTR_variant	Exon 1 of 7		XP_047303289.1
CLDN16	NM_001378492.1 link	c.-279+7591C>A	intron_variant	Intron 2 of 8		NP_001365421.1
CLDN16	NM_001378493.1 link	c.-279+32059C>A	intron_variant	Intron 1 of 7		NP_001365422.1
CLDN1	NM_021101.5 link	c.-444G>T	upstream_gene_variant		ENST00000295522.4	NP_066924.1	O95832A5JSJ9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLDN16	ENST00000468220.1 link	n.110C>A		non_coding_transcript_exon_variant	Exon 1 of 5	4
CLDN1	ENST00000295522.4 link	c.-444G>T		upstream_gene_variant		1	NM_021101.5	ENSP00000295522.3		O95832

Frequencies

GnomAD3 genomes

AF:

0.105

AC:

16041

AN:

152146

Hom.:

1014

Cov.:

show subpopulations

Gnomad AFR

AF:

0.120

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.162

Gnomad ASJ

AF:

0.105

Gnomad EAS

AF:

0.225

Gnomad SAS

AF:

0.177

Gnomad FIN

AF:

0.0626

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0774

Gnomad OTH

AF:

0.125

GnomAD4 exome

AF:

0.0962

AC:

9462

AN:

98328

Hom.:

616

Cov.:

AF XY:

0.104

AC XY:

5354

AN XY:

51650

show subpopulations

African (AFR)

AF:

0.108

AC:

AN:

824

American (AMR)

AF:

0.172

AC:

610

AN:

3550

Ashkenazi Jewish (ASJ)

AF:

0.0983

AC:

208

AN:

2116

East Asian (EAS)

AF:

0.197

AC:

613

AN:

3106

South Asian (SAS)

AF:

0.156

AC:

2521

AN:

16132

European-Finnish (FIN)

AF:

0.0595

AC:

411

AN:

6908

Middle Eastern (MID)

AF:

0.102

AC:

AN:

384

European-Non Finnish (NFE)

AF:

0.0757

AC:

4529

AN:

59856

Other (OTH)

AF:

0.0811

AC:

442

AN:

5452

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

394

789

1183

1578

1972

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

168

224

280

<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:

0.106

AC:

16077

AN:

152264

Hom.:

1018

Cov.:

AF XY:

0.109

AC XY:

8103

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.120

AC:

4979

AN:

41566

American (AMR)

AF:

0.162

AC:

2476

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.105

AC:

365

AN:

3468

East Asian (EAS)

AF:

0.226

AC:

1166

AN:

5164

South Asian (SAS)

AF:

0.177

AC:

851

AN:

4818

European-Finnish (FIN)

AF:

0.0626

AC:

665

AN:

10622

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0775

AC:

5270

AN:

68014

Other (OTH)

AF:

0.126

AC:

267

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

703

1406

2109

2812

3515

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

376

564

752

940

<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:

0.0871

Hom.:

Bravo

AF:

0.113

Asia WGS

AF:

0.200

AC:

694

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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

- -

Nov 10, 2018

GeneDx

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

-0.72

CADD

Benign

7.0

(source)

DANN

Benign

0.66

PhyloP100

-0.89

PromoterAI

0.0062

Neutral

(source)

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over