rs6809685

Positions:

• chr3-190314805-A-G

Variant summary

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

The NM_021101.5(CLDN1):​c.224-1769T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,124 control chromosomes in the GnomAD database, including 2,115 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 0.16 (2115 hom., cov: 31)
• Consequence: CLDN1 NM_021101.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83

Genes affected

CLDN1 (HGNC:2032): (claudin 1) Tight junctions represent one mode of cell-to-cell adhesion in epithelial or endothelial cell sheets, forming continuous seals around cells and serving as a physical barrier to prevent solutes and water from passing freely through the paracellular space. These junctions are comprised of sets of continuous networking strands in the outwardly facing cytoplasmic leaflet, with complementary grooves in the inwardly facing extracytoplasmic leaflet. The protein encoded by this gene, a member of the claudin family, is an integral membrane protein and a component of tight junction strands. Loss of function mutations result in neonatal ichthyosis-sclerosing cholangitis syndrome. [provided by RefSeq, Jul 2008]

CLDN16 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLDN1	NM_021101.5	c.224-1769T>C		intron_variant		ENST00000295522.4
CLDN16	NM_001378492.1	c.-445-88A>G		intron_variant
CLDN16	NM_001378493.1	c.-279+24214A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLDN1	ENST00000295522.4	c.224-1769T>C		intron_variant		1	NM_021101.5	P1

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24199 AN: 152006 Hom.: 2113 Cov.: 31

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.0466

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.0920

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.159 AC: 24218 AN: 152124 Hom.: 2115 Cov.: 31 AF XY: 0.159 AC XY: 11809 AN XY: 74386

Gnomad4 AFR AF: 0.232

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.0467

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.0920

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.159

Alfa AF: 0.139 Hom.: 2071

Bravo AF: 0.169

Asia WGS AF: 0.156 AC: 545 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.6
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs6809685; hg19: chr3-190032594;