3-190319230-C-G

Position:

• chr3-190319230-C-G

Variant summary

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

The ENST00000295522.4(CLDN1):​c.223+2754G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,112 control chromosomes in the GnomAD database, including 1,409 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 0.13 (1409 hom., cov: 32)
• Consequence: CLDN1 ENST00000295522.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.435

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLDN1	NM_021101.5	c.223+2754G>C		intron_variant		ENST00000295522.4	NP_066924.1
CLDN16	NM_001378492.1	c.-279+4171C>G		intron_variant			NP_001365421.1
CLDN16	NM_001378493.1	c.-279+28639C>G		intron_variant			NP_001365422.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLDN1	ENST00000295522.4	c.223+2754G>C		intron_variant		1	NM_021101.5	ENSP00000295522	P1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19725 AN: 151994 Hom.: 1403 Cov.: 32

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.0398

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.130 AC: 19753 AN: 152112 Hom.: 1409 Cov.: 32 AF XY: 0.126 AC XY: 9395 AN XY: 74368

Gnomad4 AFR AF: 0.190

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.0398

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.133

Alfa AF: 0.124 Hom.: 159

Bravo AF: 0.137

Asia WGS AF: 0.133 AC: 464 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.1
DANN	Benign	0.42

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: rs9839711; hg19: chr3-190037019;