7-73831234-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_001305.5(CLDN4):​c.33C>T​(p.Ile11Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000494 in 1,589,574 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 34)
Exomes 𝑓: 0.00053 ( 0 hom. )

Consequence

CLDN4
NM_001305.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -5.42
Variant links:
Genes affected
CLDN4 (HGNC:2046): (claudin 4) The protein encoded by this intronless gene belongs to the claudin family. Claudins are integral membrane proteins that are components of the epithelial cell tight junctions, which regulate movement of solutes and ions through the paracellular space. This protein is a high-affinity receptor for Clostridium perfringens enterotoxin (CPE) and may play a role in internal organ development and function during pre- and postnatal life. This gene is deleted in Williams-Beuren syndrome, a neurodevelopmental disorder affecting multiple systems. [provided by RefSeq, Sep 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
Variant 7-73831234-C-T is Benign according to our data. Variant chr7-73831234-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1676063.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-5.42 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CLDN4NM_001305.5 linkc.33C>T p.Ile11Ile synonymous_variant Exon 1 of 1 ENST00000340958.4 NP_001296.1 O14493Q75L80

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CLDN4ENST00000340958.4 linkc.33C>T p.Ile11Ile synonymous_variant Exon 1 of 1 6 NM_001305.5 ENSP00000342445.2 O14493
CLDN4ENST00000431918.1 linkc.33C>T p.Ile11Ile synonymous_variant Exon 2 of 2 2 ENSP00000388639.1 O14493
CLDN4ENST00000435050.1 linkc.33C>T p.Ile11Ile synonymous_variant Exon 2 of 2 2 ENSP00000409544.1 O14493

Frequencies

GnomAD3 genomes
AF:
0.000158
AC:
24
AN:
152248
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000238
AC:
56
AN:
235214
Hom.:
0
AF XY:
0.000285
AC XY:
36
AN XY:
126280
show subpopulations
Gnomad AFR exome
AF:
0.000188
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000375
Gnomad FIN exome
AF:
0.0000491
Gnomad NFE exome
AF:
0.000480
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000529
AC:
761
AN:
1437326
Hom.:
0
Cov.:
33
AF XY:
0.000505
AC XY:
359
AN XY:
711458
show subpopulations
Gnomad4 AFR exome
AF:
0.0000904
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000763
Gnomad4 SAS exome
AF:
0.0000607
Gnomad4 FIN exome
AF:
0.0000769
Gnomad4 NFE exome
AF:
0.000665
Gnomad4 OTH exome
AF:
0.000270
GnomAD4 genome
AF:
0.000158
AC:
24
AN:
152248
Hom.:
0
Cov.:
34
AF XY:
0.000108
AC XY:
8
AN XY:
74382
show subpopulations
Gnomad4 AFR
AF:
0.0000965
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000232
Hom.:
0
Bravo
AF:
0.000193

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Jan 01, 2022
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.43
CADD
Benign
5.1
DANN
Benign
0.92
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6

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.

Other links and lift over

dbSNP: rs146691861; hg19: chr7-73245564; COSMIC: COSV52895438; COSMIC: COSV52895438; API