rs219779

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001146079.2(CLDN14):c.243C>T(p.Arg81Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 1,613,114 control chromosomes in the GnomAD database, including 50,317 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5073 hom., cov: 33)

Exomes 𝑓: 0.24 ( 45244 hom. )

Consequence

CLDN14
NM_001146079.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.13

Publications

31 publications found

Variant links:

Genes affected

CLDN14 (HGNC:2035): (claudin 14) 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. The encoded protein also binds specifically to the WW domain of Yes-associated protein. Defects in this gene are the cause of an autosomal recessive form of nonsyndromic sensorineural deafness. It is also reported that four synonymous variants in this gene are associated with kidney stones and reduced bone mineral density. Several transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jun 2010]

CLDN14 links:

LNCTSI (HGNC:56660): (lncRNA TGF-beta/SMAD3 pathway interacting)

LNCTSI links:

CLDN14-AS1 (HGNC:55953): (CLDN14 antisense RNA 1)

CLDN14-AS1 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=-0.81).

BP6

Variant 21-36461453-G-A is Benign according to our data. Variant chr21-36461453-G-A is described in ClinVar as Benign. ClinVar VariationId is 44084.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.13 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLDN14	NM_001146079.2 link	c.243C>T	p.Arg81Arg	synonymous_variant	Exon 2 of 2	ENST00000399135.6	NP_001139551.1	O95500

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLDN14	ENST00000399135.6 link	c.243C>T	p.Arg81Arg	synonymous_variant	Exon 2 of 2	1	NM_001146079.2	ENSP00000382087.1		O95500

Frequencies

GnomAD3 genomes

AF:

0.250

AC:

37944

AN:

152062

Hom.:

5055

Cov.:

show subpopulations

Gnomad AFR

AF:

0.310

Gnomad AMI

AF:

0.126

Gnomad AMR

AF:

0.228

Gnomad ASJ

AF:

0.236

Gnomad EAS

AF:

0.00771

Gnomad SAS

AF:

0.147

Gnomad FIN

AF:

0.211

Gnomad MID

AF:

0.323

Gnomad NFE

AF:

0.251

Gnomad OTH

AF:

0.260

GnomAD2 exomes

AF:

0.212

AC:

52925

AN:

249378

AF XY:

0.210

show subpopulations

Gnomad AFR exome

AF:

0.304

Gnomad AMR exome

AF:

0.194

Gnomad ASJ exome

AF:

0.238

Gnomad EAS exome

AF:

0.00534

Gnomad FIN exome

AF:

0.206

Gnomad NFE exome

AF:

0.252

Gnomad OTH exome

AF:

0.222

GnomAD4 exome

AF:

0.242

AC:

354123

AN:

1460934

Hom.:

45244

Cov.:

AF XY:

0.239

AC XY:

173901

AN XY:

726808

show subpopulations

African (AFR)

AF:

0.309

AC:

10351

AN:

33474

American (AMR)

AF:

0.197

AC:

8822

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.236

AC:

6172

AN:

26124

East Asian (EAS)

AF:

0.00768

AC:

305

AN:

39696

South Asian (SAS)

AF:

0.158

AC:

13592

AN:

86258

European-Finnish (FIN)

AF:

0.210

AC:

11047

AN:

52552

Middle Eastern (MID)

AF:

0.249

AC:

1436

AN:

5768

European-Non Finnish (NFE)

AF:

0.259

AC:

288181

AN:

1111954

Other (OTH)

AF:

0.235

AC:

14217

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

19405

38810

58215

77620

97025

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9672

19344

29016

38688

48360

<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:

0.250

AC:

38010

AN:

152180

Hom.:

5073

Cov.:

AF XY:

0.243

AC XY:

18076

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.310

AC:

12893

AN:

41524

American (AMR)

AF:

0.228

AC:

3488

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.236

AC:

818

AN:

3472

East Asian (EAS)

AF:

0.00773

AC:

AN:

5176

South Asian (SAS)

AF:

0.148

AC:

714

AN:

4828

European-Finnish (FIN)

AF:

0.211

AC:

2238

AN:

10598

Middle Eastern (MID)

AF:

0.327

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.251

AC:

17065

AN:

67982

Other (OTH)

AF:

0.258

AC:

543

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1470

2940

4409

5879

7349

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

386

772

1158

1544

1930

<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:

0.254

Hom.:

3933

Bravo

AF:

0.251

Asia WGS

AF:

0.109

AC:

382

AN:

3478

EpiCase

AF:

0.251

EpiControl

AF:

0.251

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Arg81Arg in Exon 03 of CLDN14: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 31.1% (1163/3738) of African American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs219779). -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 01, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Autosomal recessive nonsyndromic hearing loss 29

Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.2

(source)

DANN

Benign

0.88

PhyloP100

-1.1

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over