3-190312891-A-G

Position:

chr3-190312891-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_021101.5(CLDN1):c.369T>C(p.Gly123Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.838 in 1,613,742 control chromosomes in the GnomAD database, including 567,397 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.82 ( 51537 hom., cov: 31)

Exomes 𝑓: 0.84 ( 515860 hom. )

Consequence

CLDN1
NM_021101.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -7.62

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:2037): (claudin 16) 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. It is found primarily in the kidneys, specifically in the thick ascending limb of Henle, where it acts as either an intercellular pore or ion concentration sensor to regulate the paracellular resorption of magnesium ions. Defects in this gene are a cause of primary hypomagnesemia, which is characterized by massive renal magnesium wasting with hypomagnesemia and hypercalciuria, resulting in nephrocalcinosis and renal failure. This gene and the CLDN1 gene are clustered on chromosome 3q28. [provided by RefSeq, Jun 2010]

CLDN16 links:

CLDN1 (HGNC:):

CLDN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 3-190312891-A-G is Benign according to our data. Variant chr3-190312891-A-G is described in ClinVar as [Benign]. Clinvar id is 195367.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-190312891-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-7.62 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.839 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLDN1	NM_021101.5 linkuse as main transcript	c.369T>C	p.Gly123Gly	synonymous_variant	2/4	ENST00000295522.4	NP_066924.1	O95832A5JSJ9
CLDN16	NM_001378492.1 linkuse as main transcript	c.-445-2002A>G		intron_variant			NP_001365421.1
CLDN16	NM_001378493.1 linkuse as main transcript	c.-279+22300A>G		intron_variant			NP_001365422.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLDN1	ENST00000295522.4 linkuse as main transcript	c.369T>C	p.Gly123Gly	synonymous_variant	2/4	1	NM_021101.5	ENSP00000295522.3		O95832
CLDN1	ENST00000490800.1 linkuse as main transcript	n.328T>C		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.823

AC:

125001

AN:

151954

Hom.:

51503

Cov.:

show subpopulations

Gnomad AFR

AF:

0.770

Gnomad AMI

AF:

0.814

Gnomad AMR

AF:

0.811

Gnomad ASJ

AF:

0.862

Gnomad EAS

AF:

0.833

Gnomad SAS

AF:

0.827

Gnomad FIN

AF:

0.879

Gnomad MID

AF:

0.927

Gnomad NFE

AF:

0.845

Gnomad OTH

AF:

0.823

GnomAD3 exomes

AF:

0.832

AC:

209149

AN:

251432

Hom.:

87148

AF XY:

0.836

AC XY:

113569

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.769

Gnomad AMR exome

AF:

0.784

Gnomad ASJ exome

AF:

0.864

Gnomad EAS exome

AF:

0.823

Gnomad SAS exome

AF:

0.825

Gnomad FIN exome

AF:

0.869

Gnomad NFE exome

AF:

0.848

Gnomad OTH exome

AF:

0.839

GnomAD4 exome

AF:

0.840

AC:

1227389

AN:

1461670

Hom.:

515860

Cov.:

AF XY:

0.840

AC XY:

610604

AN XY:

727148

show subpopulations

Gnomad4 AFR exome

AF:

0.769

Gnomad4 AMR exome

AF:

0.783

Gnomad4 ASJ exome

AF:

0.866

Gnomad4 EAS exome

AF:

0.850

Gnomad4 SAS exome

AF:

0.822

Gnomad4 FIN exome

AF:

0.871

Gnomad4 NFE exome

AF:

0.843

Gnomad4 OTH exome

AF:

0.838

GnomAD4 genome

AF:

0.823

AC:

125089

AN:

152072

Hom.:

51537

Cov.:

AF XY:

0.825

AC XY:

61361

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.770

Gnomad4 AMR

AF:

0.811

Gnomad4 ASJ

AF:

0.862

Gnomad4 EAS

AF:

0.833

Gnomad4 SAS

AF:

0.828

Gnomad4 FIN

AF:

0.879

Gnomad4 NFE

AF:

0.845

Gnomad4 OTH

AF:

0.818

Alfa

AF:

0.840

Hom.:

107938

Bravo

AF:

0.814

Asia WGS

AF:

0.800

AC:

2785

AN:

3478

EpiCase

AF:

0.846

EpiControl

AF:

0.851

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Sep 19, 2014	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Neonatal ichthyosis-sclerosing cholangitis syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.037

DANN

Benign

0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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