rs74824159
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_000083.3(CLCN1):c.2284+5C>T variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0246 in 1,590,352 control chromosomes in the GnomAD database, including 591 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000083.3 splice_donor_5th_base, intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CLCN1 | NM_000083.3 | c.2284+5C>T | splice_donor_5th_base_variant, intron_variant | ENST00000343257.7 | |||
CLCN1 | NR_046453.2 | n.2239+5C>T | splice_donor_5th_base_variant, intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLCN1 | ENST00000343257.7 | c.2284+5C>T | splice_donor_5th_base_variant, intron_variant | 1 | NM_000083.3 | P4 | |||
CLCN1 | ENST00000432192.6 | c.*1569+5C>T | splice_donor_5th_base_variant, intron_variant, NMD_transcript_variant | 1 | |||||
CLCN1 | ENST00000650516.2 | c.2284+5C>T | splice_donor_5th_base_variant, intron_variant | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0171 AC: 2605AN: 152110Hom.: 32 Cov.: 31
GnomAD3 exomes AF: 0.0178 AC: 4457AN: 250744Hom.: 56 AF XY: 0.0183 AC XY: 2475AN XY: 135574
GnomAD4 exome AF: 0.0254 AC: 36510AN: 1438124Hom.: 559 Cov.: 31 AF XY: 0.0250 AC XY: 17947AN XY: 716904
GnomAD4 genome ? AF: 0.0171 AC: 2605AN: 152228Hom.: 32 Cov.: 31 AF XY: 0.0154 AC XY: 1143AN XY: 74430
ClinVar
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jul 25, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia | Nov 06, 2015 | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2024 | CLCN1: BP4, BS1, BS2 - |
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 17, 2019 | This variant is associated with the following publications: (PMID: 24349310, 23739125, 11840191, 24452722, 15786415, 21221019, 22094069, 23152584, 12196568, 27614575, 27884173, 28427807, 15311340, 32117024) - |
Congenital myotonia, autosomal recessive form Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Jan 01, 2016 | This variant was classified as: Uncertain significance. The following ACMG criteria were applied in classifying this variant: BP4. - |
Batten-Turner congenital myopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Mar 06, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Congenital myotonia, autosomal recessive form;C2936781:Congenital myotonia, autosomal dominant form Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at