Genetic Variant NM_194284.3:c.-77G>A (chr8-8702322-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.-77G>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 0.356 in 1,425,858 control chromosomes in the GnomAD database, including 94,945 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 0.30 ( 7615 hom., cov: 34)

Exomes 𝑓: 0.36 ( 87330 hom. )

Consequence

CLDN23
NM_194284.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0470

Publications

13 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=-0.78).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLDN23	NM_194284.3 link	c.-77G>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.-77G>A		5_prime_UTR_variant	Exon 1 of 1	6	NM_194284.3	ENSP00000428780.1		Q96B33
ENSG00000254367	ENST00000765578.1 link	n.660+21208C>T		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.301

AC:

45752

AN:

152058

Hom.:

7619

Cov.:

show subpopulations

Gnomad AFR

AF:

0.217

Gnomad AMI

AF:

0.351

Gnomad AMR

AF:

0.239

Gnomad ASJ

AF:

0.458

Gnomad EAS

AF:

0.0488

Gnomad SAS

AF:

0.242

Gnomad FIN

AF:

0.296

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.380

Gnomad OTH

AF:

0.325

GnomAD4 exome

AF:

0.363

AC:

461869

AN:

1273682

Hom.:

87330

Cov.:

AF XY:

0.361

AC XY:

223894

AN XY:

620754

show subpopulations

African (AFR)

AF:

0.213

AC:

5587

AN:

26218

American (AMR)

AF:

0.199

AC:

4350

AN:

21848

Ashkenazi Jewish (ASJ)

AF:

0.452

AC:

8238

AN:

18220

East Asian (EAS)

AF:

0.0687

AC:

2377

AN:

34622

South Asian (SAS)

AF:

0.255

AC:

15953

AN:

62508

European-Finnish (FIN)

AF:

0.312

AC:

10305

AN:

33054

Middle Eastern (MID)

AF:

0.330

AC:

1161

AN:

3516

European-Non Finnish (NFE)

AF:

0.388

AC:

395680

AN:

1020610

Other (OTH)

AF:

0.343

AC:

18218

AN:

53086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

14530

29060

43589

58119

72649

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12732

25464

38196

50928

63660

<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:

0.301

AC:

45760

AN:

152176

Hom.:

7615

Cov.:

AF XY:

0.293

AC XY:

21818

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.217

AC:

9019

AN:

41550

American (AMR)

AF:

0.239

AC:

3648

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.458

AC:

1589

AN:

3470

East Asian (EAS)

AF:

0.0487

AC:

251

AN:

5152

South Asian (SAS)

AF:

0.241

AC:

1164

AN:

4824

European-Finnish (FIN)

AF:

0.296

AC:

3136

AN:

10606

Middle Eastern (MID)

AF:

0.337

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.380

AC:

25856

AN:

67966

Other (OTH)

AF:

0.321

AC:

679

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1665

3330

4995

6660

8325

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

454

908

1362

1816

2270

<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:

0.356

Hom.:

24492

Bravo

AF:

0.290

Asia WGS

AF:

0.148

AC:

513

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

6.1

(source)

DANN

Benign

0.93

PhyloP100

0.047

PromoterAI

0.12

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