rs3774024

Positions:

• chr3-190318025-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.223+3959T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0543 in 152,326 control chromosomes in the GnomAD database, including 320 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 0.054 (320 hom., cov: 32)
• Consequence: CLDN1 NM_021101.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.320

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLDN1	NM_021101.5	c.223+3959T>C		intron_variant		ENST00000295522.4
CLDN16	NM_001378492.1	c.-279+2966A>G		intron_variant
CLDN16	NM_001378493.1	c.-279+27434A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLDN1	ENST00000295522.4	c.223+3959T>C		intron_variant		1	NM_021101.5	P1

Frequencies

GnomAD3 genomes AF: 0.0542 AC: 8257 AN: 152208 Hom.: 318 Cov.: 32

Gnomad AFR AF: 0.0442

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.0282

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.0954

Gnomad FIN AF: 0.0180

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0460

Gnomad OTH AF: 0.0726

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

GnomAD4 genome AF: 0.0543 AC: 8273 AN: 152326 Hom.: 320 Cov.: 32 AF XY: 0.0554 AC XY: 4130 AN XY: 74486

Gnomad4 AFR AF: 0.0441

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.0282

Gnomad4 EAS AF: 0.145

Gnomad4 SAS AF: 0.0957

Gnomad4 FIN AF: 0.0180

Gnomad4 NFE AF: 0.0461

Gnomad4 OTH AF: 0.0756

Alfa AF: 0.0515 Hom.: 265

Bravo AF: 0.0610

Asia WGS AF: 0.129 AC: 449 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.69

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: rs3774024; hg19: chr3-190035814;