dbSNP rs10513681: CLDN11:c.391+193T>C (chr3-170423520-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_005602.6(CLDN11):c.391+193T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0312 in 580,924 control chromosomes in the GnomAD database, including 1,056 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 0.064 ( 739 hom., cov: 32)

Exomes 𝑓: 0.020 ( 317 hom. )

Consequence

CLDN11
NM_005602.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0280

Publications

2 publications found

Variant links:

Genes affected

CLDN11 (HGNC:8514): (claudin 11) 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 a major component of central nervous system (CNS) myelin and plays an important role in regulating proliferation and migration of oligodendrocytes. Mouse studies showed that the gene deficiency results in deafness and loss of the Sertoli cell epithelial phenotype in the testis. This protein is a tight junction protein at the human blood-testis barrier (BTB), and the BTB disruption is related to a dysfunction of this gene. Alternatively spliced transcript variants encoding different isoforms have been identified.[provided by RefSeq, Aug 2010]

CLDN11 Gene-Disease associations (from GenCC):

leukodystrophy, hypomyelinating, 22
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

CLDN11 links:

ENSG00000285218 (HGNC:):

ENSG00000285218 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=-0.81).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLDN11	NM_005602.6 link	c.391+193T>C		intron_variant	Intron 2 of 2	ENST00000064724.8	NP_005593.2	O75508
CLDN11	NM_001185056.2 link	c.139+193T>C		intron_variant	Intron 2 of 2		NP_001171985.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLDN11	ENST00000064724.8 link	c.391+193T>C		intron_variant	Intron 2 of 2	1	NM_005602.6	ENSP00000064724.4		O75508
ENSG00000285218	ENST00000486975.1 link	c.391+193T>C		intron_variant	Intron 2 of 3	2		ENSP00000417434.1		B4DFI2

Frequencies

GnomAD3 genomes

AF:

0.0637

AC:

9685

AN:

152140

Hom.:

736

Cov.:

show subpopulations

Gnomad AFR

AF:

0.183

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0719

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0143

Gnomad FIN

AF:

0.00471

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.0112

Gnomad OTH

AF:

0.0512

GnomAD4 exome

AF:

0.0196

AC:

8397

AN:

428666

Hom.:

317

Cov.:

AF XY:

0.0186

AC XY:

4136

AN XY:

222724

show subpopulations

African (AFR)

AF:

0.178

AC:

2200

AN:

12344

American (AMR)

AF:

0.0916

AC:

1689

AN:

18440

Ashkenazi Jewish (ASJ)

AF:

0.00511

AC:

AN:

13124

East Asian (EAS)

AF:

0.000229

AC:

AN:

30540

South Asian (SAS)

AF:

0.0178

AC:

665

AN:

37326

European-Finnish (FIN)

AF:

0.00704

AC:

204

AN:

28960

Middle Eastern (MID)

AF:

0.0240

AC:

AN:

2080

European-Non Finnish (NFE)

AF:

0.0108

AC:

2827

AN:

260752

Other (OTH)

AF:

0.0274

AC:

688

AN:

25100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

362

724

1087

1449

1811

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0638

AC:

9712

AN:

152258

Hom.:

739

Cov.:

AF XY:

0.0627

AC XY:

4667

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.183

AC:

7603

AN:

41508

American (AMR)

AF:

0.0719

AC:

1101

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00432

AC:

AN:

3470

East Asian (EAS)

AF:

0.000579

AC:

AN:

5184

South Asian (SAS)

AF:

0.0139

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00471

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0112

AC:

764

AN:

68034

Other (OTH)

AF:

0.0507

AC:

107

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

405

810

1216

1621

2026

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0217

Hom.:

Bravo

AF:

0.0759

Asia WGS

AF:

0.0240

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.6

(source)

DANN

Benign

0.81

PhyloP100

-0.028

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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rs10513681

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