Genetic Variant CLDN24:p.Val137Ile (chr4-183322018-C-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001185149.1(CLDN24):c.409G>A(p.Val137Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000299 in 1,613,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00029 ( 0 hom. )

Consequence

CLDN24
NM_001185149.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.52

Publications

2 publications found

Variant links:

Genes affected

CLDN24 (HGNC:37200): (claudin 24) This gene encodes a member of the claudin family. Claudins are integral membrane proteins and components of tight junction strands. Tight junction strands serve as a physical barrier to prevent solutes and water from passing freely through the paracellular space between epithelial or endothelial cell sheets, and also play critical roles in maintaining cell polarity and signal transductions. The protein encoded by this gene is 75% identical to the mouse homolog. This gene is upstream of the CLDN22 gene, which overlaps the WWC2 gene on the opposite strand in the genome.[provided by RefSeq, Aug 2010]

CLDN24 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.31783766).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001185149.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN24	NM_001185149.1	MANE Select	c.409G>A	p.Val137Ile	missense	Exon 1 of 1	NP_001172078.1	A6NM45

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN24	ENST00000541814.1	TSL:6 MANE Select	c.409G>A	p.Val137Ile	missense	Exon 1 of 1	ENSP00000438400.1	A6NM45

Frequencies

GnomAD3 genomes

AF:

0.000388

AC:

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000604

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000470

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000334

AC:

AN:

245816

AF XY:

0.000329

show subpopulations

Gnomad AFR exome

AF:

0.000392

Gnomad AMR exome

AF:

0.000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000928

Gnomad NFE exome

AF:

0.000564

Gnomad OTH exome

AF:

0.000332

GnomAD4 exome

AF:

0.000290

AC:

424

AN:

1461430

Hom.:

Cov.:

AF XY:

0.000283

AC XY:

206

AN XY:

726980

show subpopulations

African (AFR)

AF:

0.000478

AC:

AN:

33462

American (AMR)

AF:

0.000291

AC:

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26118

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86188

European-Finnish (FIN)

AF:

0.0000374

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.000335

AC:

372

AN:

1111742

Other (OTH)

AF:

0.000315

AC:

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

100

134

167

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000388

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.000376

AC XY:

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.000602

AC:

AN:

41536

American (AMR)

AF:

0.0000654

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000208

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000471

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000812

Hom.:

Bravo

AF:

0.000457

ExAC

AF:

0.000407

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.85

M_CAP

Benign

0.042

MetaRNN

Benign

0.32

MetaSVM

Uncertain

0.69

MutationAssessor

Uncertain

2.3

PhyloP100

4.5

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.87

REVEL

Uncertain

0.46

Sift

Benign

0.066

Sift4G

Benign

0.073

Vest4

0.24

MutPred

0.78

Loss of helix (P = 0.1299)

MVP

0.51

MPC

1.5

ClinPred

0.28

GERP RS

4.9

PromoterAI

-0.0088

Neutral

(source)

Varity_R

0.17

gMVP

0.44

Mutation Taster

=96/4

polymorphism

(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