rs6444931

Variant names:

• chr3-170445686-G-A
• rs6444931
• ENST00000486975.1:c.391+22359G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-170445686-G-A
• chr3-170445686-G-C
• chr3-170445686-G-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+22359G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.848 in 152,064 control chromosomes in the GnomAD database, including 54,764 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 0.85 (54764 hom., cov: 30)
• Consequence: ENSG00000285218 ENST00000486975.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74
• Publications: 9 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 = 0.894 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+22359G>A		intron	N/A	ENSP00000417434.1	B4DFI2
	ENSG00000285218	ENST00000471373.5	TSL:4	n.259-14613G>A		intron	N/A
	CLDN11	ENST00000488989.1	TSL:4	n.156+8066G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.848 AC: 128892 AN: 151946 Hom.: 54713 Cov.: 30

Gnomad AFR AF: 0.842

Gnomad AMI AF: 0.836

Gnomad AMR AF: 0.876

Gnomad ASJ AF: 0.899

Gnomad EAS AF: 0.779

Gnomad SAS AF: 0.917

Gnomad FIN AF: 0.878

Gnomad MID AF: 0.876

Gnomad NFE AF: 0.838

Gnomad OTH AF: 0.861

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

GnomAD4 genome AF: 0.848 AC: 128997 AN: 152064 Hom.: 54764 Cov.: 30 AF XY: 0.852 AC XY: 63355 AN XY: 74328

African (AFR) AF: 0.843 AC: 34921 AN: 41446

American (AMR) AF: 0.876 AC: 13386 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.899 AC: 3122 AN: 3472

East Asian (EAS) AF: 0.780 AC: 4036 AN: 5176

South Asian (SAS) AF: 0.917 AC: 4413 AN: 4814

European-Finnish (FIN) AF: 0.878 AC: 9268 AN: 10558

Middle Eastern (MID) AF: 0.870 AC: 254 AN: 292

European-Non Finnish (NFE) AF: 0.838 AC: 57013 AN: 67998

Other (OTH) AF: 0.862 AC: 1823 AN: 2114

Alfa AF: 0.844 Hom.: 97669

Bravo AF: 0.846

Asia WGS AF: 0.879 AC: 3059 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	0.17
DANN	Benign	0.56
PhyloP100		-1.7
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: rs6444931; hg19: chr3-170163474;