chr3-190310163-C-T
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong
The NM_021101.5(CLDN1):c.473+6G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000364 in 1,610,712 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0015 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00024 ( 3 hom. )
Consequence
CLDN1
NM_021101.5 splice_donor_region, intron
NM_021101.5 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.00009393
2
Clinical Significance
Conservation
PhyloP100: -0.158
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
?
Variant 3-190310163-C-T is Benign according to our data. Variant chr3-190310163-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 196505.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CLDN1 | NM_021101.5 | c.473+6G>A | splice_donor_region_variant, intron_variant | ENST00000295522.4 | |||
CLDN16 | NM_001378492.1 | c.-445-4730C>T | intron_variant | ||||
CLDN16 | NM_001378493.1 | c.-279+19572C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLDN1 | ENST00000295522.4 | c.473+6G>A | splice_donor_region_variant, intron_variant | 1 | NM_021101.5 | P1 | |||
CLDN1 | ENST00000490800.1 | downstream_gene_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00147 AC: 223AN: 152140Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.000478 AC: 120AN: 251222Hom.: 1 AF XY: 0.000346 AC XY: 47AN XY: 135792
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GnomAD4 exome AF: 0.000243 AC: 355AN: 1458454Hom.: 3 Cov.: 29 AF XY: 0.000236 AC XY: 171AN XY: 725786
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GnomAD4 genome ? AF: 0.00152 AC: 231AN: 152258Hom.: 1 Cov.: 33 AF XY: 0.00154 AC XY: 115AN XY: 74448
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 22, 2017 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 14, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at