3-170435395-C-T

Position:

• chr3-170435395-C-T

Variant summary

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

The ENST00000477531.3(CLDN11):​n.600+432C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 151,850 control chromosomes in the GnomAD database, including 13,408 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 0.41 (13408 hom., cov: 31)
• Consequence: CLDN11 ENST00000477531.3 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.65

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLDN11	ENST00000477531.3	n.600+432C>T		intron_variant, non_coding_transcript_variant		3
CLDN11	ENST00000643053.1	n.662+432C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62129 AN: 151732 Hom.: 13403 Cov.: 31

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.377

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.409 AC: 62141 AN: 151850 Hom.: 13408 Cov.: 31 AF XY: 0.410 AC XY: 30419 AN XY: 74200

Gnomad4 AFR AF: 0.286

Gnomad4 AMR AF: 0.356

Gnomad4 ASJ AF: 0.374

Gnomad4 EAS AF: 0.333

Gnomad4 SAS AF: 0.484

Gnomad4 FIN AF: 0.534

Gnomad4 NFE AF: 0.481

Gnomad4 OTH AF: 0.378

Alfa AF: 0.403 Hom.: 2937

Bravo AF: 0.390

Asia WGS AF: 0.427 AC: 1485 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.0050
DANN	Benign	0.64

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7610584; hg19: chr3-170153183;