Genetic Variant CLDN23:c.-11G>A (chr8-8702388-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_194284.3(CLDN23):c.-11G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 1,473,330 control chromosomes in the GnomAD database, including 51,707 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.24 ( 4975 hom., cov: 33)

Exomes 𝑓: 0.26 ( 46732 hom. )

Consequence

CLDN23
NM_194284.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.463

Publications

14 publications found

Variant links:

Genes affected

CLDN23 (HGNC:17591): (claudin 23) 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. This gene is expressed in germinal center B-cells, placenta and stomach as well as in colon tumor. This gene is down-regulated in intestinal type gastric cancer. [provided by RefSeq, Aug 2010]

CLDN23 links:

ENSG00000254367 (HGNC:):

ENSG00000254367 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLDN23	NM_194284.3 link	c.-11G>A		5_prime_UTR_variant	Exon 1 of 1	ENST00000519106.2	NP_919260.2	Q96B33

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLDN23	ENST00000519106.2 link	c.-11G>A		5_prime_UTR_variant	Exon 1 of 1	6	NM_194284.3	ENSP00000428780.1		Q96B33
ENSG00000254367	ENST00000765578.1 link	n.660+21142C>T		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.243

AC:

36893

AN:

152058

Hom.:

4961

Cov.:

show subpopulations

Gnomad AFR

AF:

0.155

Gnomad AMI

AF:

0.315

Gnomad AMR

AF:

0.295

Gnomad ASJ

AF:

0.205

Gnomad EAS

AF:

0.444

Gnomad SAS

AF:

0.395

Gnomad FIN

AF:

0.345

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.244

Gnomad OTH

AF:

0.223

GnomAD2 exomes

AF:

0.308

AC:

38852

AN:

126026

AF XY:

0.306

show subpopulations

Gnomad AFR exome

AF:

0.159

Gnomad AMR exome

AF:

0.402

Gnomad ASJ exome

AF:

0.219

Gnomad EAS exome

AF:

0.443

Gnomad FIN exome

AF:

0.350

Gnomad NFE exome

AF:

0.259

Gnomad OTH exome

AF:

0.309

GnomAD4 exome

AF:

0.261

AC:

344297

AN:

1321154

Hom.:

46732

Cov.:

AF XY:

0.264

AC XY:

170641

AN XY:

646484

show subpopulations

African (AFR)

AF:

0.146

AC:

3868

AN:

26506

American (AMR)

AF:

0.372

AC:

9879

AN:

26544

Ashkenazi Jewish (ASJ)

AF:

0.201

AC:

3786

AN:

18858

East Asian (EAS)

AF:

0.410

AC:

14050

AN:

34228

South Asian (SAS)

AF:

0.389

AC:

25741

AN:

66214

European-Finnish (FIN)

AF:

0.335

AC:

14338

AN:

42788

Middle Eastern (MID)

AF:

0.236

AC:

859

AN:

3636

European-Non Finnish (NFE)

AF:

0.246

AC:

257372

AN:

1048210

Other (OTH)

AF:

0.266

AC:

14404

AN:

54170

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

13085

26171

39256

52342

65427

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9308

18616

27924

37232

46540

<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:

0.243

AC:

36945

AN:

152176

Hom.:

4975

Cov.:

AF XY:

0.251

AC XY:

18650

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.156

AC:

6464

AN:

41544

American (AMR)

AF:

0.296

AC:

4527

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.205

AC:

709

AN:

3466

East Asian (EAS)

AF:

0.443

AC:

2276

AN:

5132

South Asian (SAS)

AF:

0.395

AC:

1906

AN:

4822

European-Finnish (FIN)

AF:

0.345

AC:

3657

AN:

10610

Middle Eastern (MID)

AF:

0.177

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.244

AC:

16578

AN:

67974

Other (OTH)

AF:

0.231

AC:

489

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1415

2831

4246

5662

7077

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

404

808

1212

1616

2020

<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:

0.164

Hom.:

415

Bravo

AF:

0.235

Asia WGS

AF:

0.436

AC:

1514

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

(source)

DANN

Benign

0.97

PhyloP100

-0.46

PromoterAI

-0.016

Neutral

(source)

Mutation Taster

=300/0

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

Computational scores

Splicing

Publications

Other links and lift over