Variant chr3-190322219-C-G 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.-13G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0797 in 1,612,174 control chromosomes in the GnomAD database, including 5,555 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.066 ( 385 hom., cov: 33)

Exomes 𝑓: 0.081 ( 5170 hom. )

Consequence

CLDN1
NM_021101.5 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.154

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=-0.59).

BP6

Variant 3-190322219-C-G is Benign according to our data. Variant chr3-190322219-C-G is described in ClinVar as [Benign]. Clinvar id is 261401.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0849 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
CLDN1	NM_021101.5 linkuse as main transcript	c.-13G>C	5_prime_UTR_variant	1/4	ENST00000295522.4
CLDN16	NM_001378492.1 linkuse as main transcript	c.-279+7160C>G	intron_variant
CLDN16	NM_001378493.1 linkuse as main transcript	c.-279+31628C>G	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLDN1	ENST00000295522.4 linkuse as main transcript	c.-13G>C		5_prime_UTR_variant	1/4	1	NM_021101.5	P1

Frequencies

GnomAD3 genomes

AF:

0.0659

AC:

10033

AN:

152194

Hom.:

386

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0336

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.0723

Gnomad ASJ

AF:

0.0323

Gnomad EAS

AF:

0.0143

Gnomad SAS

AF:

0.0512

Gnomad FIN

AF:

0.0929

Gnomad MID

AF:

0.0605

Gnomad NFE

AF:

0.0867

Gnomad OTH

AF:

0.0779

GnomAD3 exomes

AF:

0.0666

AC:

16468

AN:

247120

Hom.:

664

AF XY:

0.0685

AC XY:

9192

AN XY:

134224

show subpopulations

Gnomad AFR exome

AF:

0.0317

Gnomad AMR exome

AF:

0.0471

Gnomad ASJ exome

AF:

0.0382

Gnomad EAS exome

AF:

0.0139

Gnomad SAS exome

AF:

0.0538

Gnomad FIN exome

AF:

0.0928

Gnomad NFE exome

AF:

0.0866

Gnomad OTH exome

AF:

0.0803

GnomAD4 exome

AF:

0.0811

AC:

118419

AN:

1459862

Hom.:

5170

Cov.:

AF XY:

0.0804

AC XY:

58384

AN XY:

726270

show subpopulations

Gnomad4 AFR exome

AF:

0.0322

Gnomad4 AMR exome

AF:

0.0511

Gnomad4 ASJ exome

AF:

0.0348

Gnomad4 EAS exome

AF:

0.00995

Gnomad4 SAS exome

AF:

0.0533

Gnomad4 FIN exome

AF:

0.0890

Gnomad4 NFE exome

AF:

0.0894

Gnomad4 OTH exome

AF:

0.0778

GnomAD4 genome

AF:

0.0659

AC:

10031

AN:

152312

Hom.:

385

Cov.:

AF XY:

0.0648

AC XY:

4827

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0335

Gnomad4 AMR

AF:

0.0721

Gnomad4 ASJ

AF:

0.0323

Gnomad4 EAS

AF:

0.0141

Gnomad4 SAS

AF:

0.0512

Gnomad4 FIN

AF:

0.0929

Gnomad4 NFE

AF:

0.0867

Gnomad4 OTH

AF:

0.0781

Alfa

AF:

0.0713

Hom.:

Bravo

AF:

0.0644

Asia WGS

AF:

0.0490

AC:

171

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 10, 2016	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.85

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