rs10513681

Positions:

• chr3-170423520-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0280

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]

ENSG00000285218 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
CLDN11	NM_005602.6	c.391+193T>C		intron_variant		ENST00000064724.8	NP_005593.2
CLDN11	NM_001185056.2	c.139+193T>C		intron_variant			NP_001171985.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLDN11	ENST00000064724.8	c.391+193T>C		intron_variant		1	NM_005602.6	ENSP00000064724.4
ENSG00000285218	ENST00000486975.1	c.391+193T>C		intron_variant		2		ENSP00000417434.1

Frequencies

GnomAD3 genomes AF: 0.0637 AC: 9685 AN: 152140 Hom.: 736 Cov.: 32

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.: 5 AF XY: 0.0186 AC XY: 4136 AN XY: 222724

Gnomad4 AFR exome AF: 0.178

Gnomad4 AMR exome AF: 0.0916

Gnomad4 ASJ exome AF: 0.00511

Gnomad4 EAS exome AF: 0.000229

Gnomad4 SAS exome AF: 0.0178

Gnomad4 FIN exome AF: 0.00704

Gnomad4 NFE exome AF: 0.0108

Gnomad4 OTH exome AF: 0.0274

GnomAD4 genome AF: 0.0638 AC: 9712 AN: 152258 Hom.: 739 Cov.: 32 AF XY: 0.0627 AC XY: 4667 AN XY: 74454

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.0719

Gnomad4 ASJ AF: 0.00432

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0139

Gnomad4 FIN AF: 0.00471

Gnomad4 NFE AF: 0.0112

Gnomad4 OTH AF: 0.0507

Alfa AF: 0.0282 Hom.: 54

Bravo AF: 0.0759

Asia WGS AF: 0.0240 AC: 85 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
DANN	Benign	0.81

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

LitVar

Other links and lift over

dbSNP: rs10513681; hg19: chr3-170141308;