Variant 3-190308175-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_021101.5(CLDN1):c.*102G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 1,364,970 control chromosomes in the GnomAD database, including 21,886 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1813 hom., cov: 32)

Exomes 𝑓: 0.18 ( 20073 hom. )

Consequence

CLDN1
NM_021101.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.172

Variant links:

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]

CLDN1 links:

CLDN16 (HGNC:):

CLDN16 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 3-190308175-C-T is Benign according to our data. Variant chr3-190308175-C-T is described in ClinVar as [Benign]. Clinvar id is 1183502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
CLDN1	NM_021101.5 linkuse as main transcript	c.*102G>A	3_prime_UTR_variant	4/4	ENST00000295522.4
CLDN16	NM_001378492.1 linkuse as main transcript	c.-445-6718C>T	intron_variant
CLDN16	NM_001378493.1 linkuse as main transcript	c.-279+17584C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLDN1	ENST00000295522.4 linkuse as main transcript	c.*102G>A		3_prime_UTR_variant	4/4	1	NM_021101.5	P1

Frequencies

GnomAD3 genomes

AF:

0.145

AC:

22005

AN:

152004

Hom.:

1812

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0825

Gnomad AMI

AF:

0.278

Gnomad AMR

AF:

0.110

Gnomad ASJ

AF:

0.204

Gnomad EAS

AF:

0.0895

Gnomad SAS

AF:

0.137

Gnomad FIN

AF:

0.158

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.187

Gnomad OTH

AF:

0.158

GnomAD4 exome

AF:

0.178

AC:

215347

AN:

1212848

Hom.:

20073

Cov.:

AF XY:

0.178

AC XY:

109513

AN XY:

615524

show subpopulations

Gnomad4 AFR exome

AF:

0.0767

Gnomad4 AMR exome

AF:

0.0839

Gnomad4 ASJ exome

AF:

0.194

Gnomad4 EAS exome

AF:

0.102

Gnomad4 SAS exome

AF:

0.142

Gnomad4 FIN exome

AF:

0.159

Gnomad4 NFE exome

AF:

0.193

Gnomad4 OTH exome

AF:

0.170

GnomAD4 genome

AF:

0.145

AC:

22010

AN:

152122

Hom.:

1813

Cov.:

AF XY:

0.143

AC XY:

10648

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.0824

Gnomad4 AMR

AF:

0.110

Gnomad4 ASJ

AF:

0.204

Gnomad4 EAS

AF:

0.0894

Gnomad4 SAS

AF:

0.138

Gnomad4 FIN

AF:

0.158

Gnomad4 NFE

AF:

0.187

Gnomad4 OTH

AF:

0.158

Alfa

AF:

0.171

Hom.:

508

Bravo

AF:

0.137

Asia WGS

AF:

0.124

AC:

429

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

7.8

DANN

Benign

0.40

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over