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. Variant got -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

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]

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 = 0.894 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000285218	ENST00000486975.1	c.391+22359G>A		intron_variant	Intron 2 of 3	2		ENSP00000417434.1
ENSG00000285218	ENST00000471373.5	n.259-14613G>A		intron_variant	Intron 2 of 3	4
CLDN11	ENST00000488989.1	n.156+8066G>A		intron_variant	Intron 1 of 1	4
CLDN11	ENST00000643053.1	n.1032+8066G>A		intron_variant	Intron 5 of 5

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

Gnomad4 AFR AF: 0.843

Gnomad4 AMR AF: 0.876

Gnomad4 ASJ AF: 0.899

Gnomad4 EAS AF: 0.780

Gnomad4 SAS AF: 0.917

Gnomad4 FIN AF: 0.878

Gnomad4 NFE AF: 0.838

Gnomad4 OTH AF: 0.862

Alfa AF: 0.841 Hom.: 61277

Bravo AF: 0.846

Asia WGS AF: 0.879 AC: 3059 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	0.17
DANN	Benign	0.56

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6444931; hg19: chr3-170163474;