dbSNP rs6460054: CLDN3:c.-155A>G (chr7-73770204-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001306.4(CLDN3):c.-155A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 1,154,684 control chromosomes in the GnomAD database, including 135,534 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 0.51 ( 20235 hom., cov: 34)

Exomes 𝑓: 0.48 ( 115299 hom. )

Consequence

CLDN3
NM_001306.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.30

Publications

10 publications found

Variant links:

Genes affected

CLDN3 (HGNC:2045): (claudin 3) 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 intronless gene, a member of the claudin family, is an integral membrane protein and a component of tight junction strands. It is also a low-affinity receptor for Clostridium perfringens enterotoxin, and shares aa sequence similarity with a putative apoptosis-related protein found in rat. [provided by RefSeq, Jul 2008]

CLDN3 links:

Genome browser will be placed here

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=-0.79).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLDN3	NM_001306.4 link	c.-155A>G		5_prime_UTR_variant	Exon 1 of 1	ENST00000395145.3	NP_001297.1	O15551Q75L79

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLDN3	ENST00000395145.3 link	c.-155A>G		5_prime_UTR_variant	Exon 1 of 1	6	NM_001306.4	ENSP00000378577.2		O15551

Frequencies

GnomAD3 genomes

AF:

0.513

AC:

78022

AN:

151962

Hom.:

20237

Cov.:

show subpopulations

Gnomad AFR

AF:

0.559

Gnomad AMI

AF:

0.447

Gnomad AMR

AF:

0.548

Gnomad ASJ

AF:

0.553

Gnomad EAS

AF:

0.513

Gnomad SAS

AF:

0.549

Gnomad FIN

AF:

0.473

Gnomad MID

AF:

0.558

Gnomad NFE

AF:

0.480

Gnomad OTH

AF:

0.532

GnomAD4 exome

AF:

0.477

AC:

478548

AN:

1002616

Hom.:

115299

Cov.:

AF XY:

0.479

AC XY:

234540

AN XY:

489274

show subpopulations

African (AFR)

AF:

0.565

AC:

10993

AN:

19456

American (AMR)

AF:

0.542

AC:

4950

AN:

9128

Ashkenazi Jewish (ASJ)

AF:

0.544

AC:

8222

AN:

15106

East Asian (EAS)

AF:

0.448

AC:

11823

AN:

26416

South Asian (SAS)

AF:

0.559

AC:

24920

AN:

44570

European-Finnish (FIN)

AF:

0.479

AC:

13834

AN:

28892

Middle Eastern (MID)

AF:

0.586

AC:

1755

AN:

2996

European-Non Finnish (NFE)

AF:

0.468

AC:

380266

AN:

813156

Other (OTH)

AF:

0.508

AC:

21785

AN:

42896

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

11839

23678

35518

47357

59196

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11564

23128

34692

46256

57820

<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:

0.513

AC:

78033

AN:

152068

Hom.:

20235

Cov.:

AF XY:

0.514

AC XY:

38246

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.559

AC:

23195

AN:

41510

American (AMR)

AF:

0.548

AC:

8365

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.553

AC:

1921

AN:

3472

East Asian (EAS)

AF:

0.512

AC:

2634

AN:

5142

South Asian (SAS)

AF:

0.548

AC:

2645

AN:

4826

European-Finnish (FIN)

AF:

0.473

AC:

5007

AN:

10594

Middle Eastern (MID)

AF:

0.555

AC:

161

AN:

290

European-Non Finnish (NFE)

AF:

0.480

AC:

32584

AN:

67930

Other (OTH)

AF:

0.526

AC:

1113

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

2033

4067

6100

8134

10167

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

696

1392

2088

2784

3480

<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:

0.483

Hom.:

2253

Bravo

AF:

0.522

Asia WGS

AF:

0.500

AC:

1728

AN:

3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

6.5

(source)

DANN

Benign

0.40

PhyloP100

-1.3

PromoterAI

0.0048

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