dbSNP rs2717701: CLDN6:c.-21-125C>G (chr16-3016167-G-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_021195.5(CLDN6):c.-21-125C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 813,862 control chromosomes in the GnomAD database, including 58,055 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 0.36 ( 10078 hom., cov: 33)

Exomes 𝑓: 0.37 ( 47977 hom. )

Consequence

CLDN6
NM_021195.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.811

Publications

8 publications found

Variant links:

Genes affected

CLDN6 (HGNC:2048): (claudin 6) 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. This gene encodes a component of tight junction strands, which is a member of the claudin family. The protein is an integral membrane protein and is one of the entry cofactors for hepatitis C virus. The gene methylation may be involved in esophageal tumorigenesis. This gene is adjacent to another family member CLDN9 on chromosome 16.[provided by RefSeq, Aug 2010]

CLDN6 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=-0.85).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLDN6	NM_021195.5 link	c.-21-125C>G		intron_variant	Intron 1 of 1	ENST00000328796.5	NP_067018.2	P56747

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CLDN6	ENST00000328796.5 link	c.-21-125C>G	intron_variant	Intron 1 of 1	1	NM_021195.5	ENSP00000328674.4	P56747
CLDN6	ENST00000396925.1 link	c.-21-125C>G	intron_variant	Intron 2 of 2	5		ENSP00000380131.1	P56747
CLDN6	ENST00000572154.1 link	c.-21-125C>G	intron_variant	Intron 1 of 2	3		ENSP00000458783.1	I3L1E7

Frequencies

GnomAD3 genomes

AF:

0.357

AC:

54273

AN:

152014

Hom.:

10071

Cov.:

show subpopulations

Gnomad AFR

AF:

0.305

Gnomad AMI

AF:

0.441

Gnomad AMR

AF:

0.383

Gnomad ASJ

AF:

0.418

Gnomad EAS

AF:

0.187

Gnomad SAS

AF:

0.243

Gnomad FIN

AF:

0.343

Gnomad MID

AF:

0.408

Gnomad NFE

AF:

0.402

Gnomad OTH

AF:

0.366

GnomAD4 exome

AF:

0.374

AC:

247547

AN:

661730

Hom.:

47977

AF XY:

0.371

AC XY:

125049

AN XY:

337068

show subpopulations

African (AFR)

AF:

0.304

AC:

4973

AN:

16338

American (AMR)

AF:

0.385

AC:

7527

AN:

19554

Ashkenazi Jewish (ASJ)

AF:

0.417

AC:

6290

AN:

15084

East Asian (EAS)

AF:

0.205

AC:

6557

AN:

31956

South Asian (SAS)

AF:

0.266

AC:

13338

AN:

50094

European-Finnish (FIN)

AF:

0.354

AC:

11954

AN:

33732

Middle Eastern (MID)

AF:

0.397

AC:

1100

AN:

2768

European-Non Finnish (NFE)

AF:

0.400

AC:

183887

AN:

459352

Other (OTH)

AF:

0.363

AC:

11921

AN:

32852

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

8095

16190

24286

32381

40476

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3630

7260

10890

14520

18150

<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:

0.357

AC:

54292

AN:

152132

Hom.:

10078

Cov.:

AF XY:

0.351

AC XY:

26064

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.304

AC:

12630

AN:

41486

American (AMR)

AF:

0.383

AC:

5852

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.418

AC:

1449

AN:

3468

East Asian (EAS)

AF:

0.187

AC:

970

AN:

5176

South Asian (SAS)

AF:

0.243

AC:

1176

AN:

4830

European-Finnish (FIN)

AF:

0.343

AC:

3633

AN:

10586

Middle Eastern (MID)

AF:

0.414

AC:

121

AN:

292

European-Non Finnish (NFE)

AF:

0.402

AC:

27293

AN:

67970

Other (OTH)

AF:

0.362

AC:

766

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1838

3676

5514

7352

9190

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

518

1036

1554

2072

2590

<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:

0.391

Hom.:

1642

Bravo

AF:

0.360

Asia WGS

AF:

0.209

AC:

729

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.77

(source)

DANN

Benign

0.37

PhyloP100

-0.81

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

Computational scores

Splicing

Publications

Other links and lift over