3-170435395-C-T

Variant names:

• chr3-170435395-C-T
• rs7610584
• ENST00000486975.1:c.391+12068C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000486975.1(ENSG00000285218):​c.391+12068C>T variant causes a intron 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: ENSG00000285218 ENST00000486975.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.65
• Publications: 4 publications found

Genes affected

ENSG00000285218 (HGNC:):

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)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000486975.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000285218	ENST00000486975.1	TSL:2	c.391+12068C>T		intron	N/A	ENSP00000417434.1	B4DFI2
	CLDN11	ENST00000970096.1		c.*26-1856C>T		intron	N/A	ENSP00000640155.1
	ENSG00000285218	ENST00000471373.5	TSL:4	n.258+12068C>T		intron	N/A

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

African (AFR) AF: 0.286 AC: 11842 AN: 41406

American (AMR) AF: 0.356 AC: 5439 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1299 AN: 3472

East Asian (EAS) AF: 0.333 AC: 1709 AN: 5130

South Asian (SAS) AF: 0.484 AC: 2330 AN: 4816

European-Finnish (FIN) AF: 0.534 AC: 5633 AN: 10550

Middle Eastern (MID) AF: 0.274 AC: 80 AN: 292

European-Non Finnish (NFE) AF: 0.481 AC: 32627 AN: 67902

Other (OTH) AF: 0.378 AC: 800 AN: 2114

Alfa AF: 0.437 Hom.: 6317

Bravo AF: 0.390

Asia WGS AF: 0.427 AC: 1485 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.0050
DANN	Benign	0.64
PhyloP100		-3.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs7610584; hg19: chr3-170153183;