rs141945240
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_000083.3(CLCN1):āc.1815T>Cā(p.Val605=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000265 in 1,614,166 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.00078 ( 0 hom., cov: 32)
Exomes š: 0.00021 ( 1 hom. )
Consequence
CLCN1
NM_000083.3 synonymous
NM_000083.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.976
Genes affected
CLCN1 (HGNC:2019): (chloride voltage-gated channel 1) The CLCN family of voltage-dependent chloride channel genes comprises nine members (CLCN1-7, Ka and Kb) which demonstrate quite diverse functional characteristics while sharing significant sequence homology. The protein encoded by this gene regulates the electric excitability of the skeletal muscle membrane. Mutations in this gene cause two forms of inherited human muscle disorders: recessive generalized myotonia congenita (Becker) and dominant myotonia (Thomsen). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.47).
BP6
?
Variant 7-143342390-T-C is Benign according to our data. Variant chr7-143342390-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 392559.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.976 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CLCN1 | NM_000083.3 | c.1815T>C | p.Val605= | synonymous_variant | 16/23 | ENST00000343257.7 | |
CLCN1 | NR_046453.2 | n.1770T>C | non_coding_transcript_exon_variant | 15/22 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLCN1 | ENST00000343257.7 | c.1815T>C | p.Val605= | synonymous_variant | 16/23 | 1 | NM_000083.3 | P4 | |
CLCN1 | ENST00000432192.6 | c.*1100T>C | 3_prime_UTR_variant, NMD_transcript_variant | 16/23 | 1 | ||||
CLCN1 | ENST00000650516.2 | c.1815T>C | p.Val605= | synonymous_variant | 16/23 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000782 AC: 119AN: 152170Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000370 AC: 93AN: 251462Hom.: 0 AF XY: 0.000250 AC XY: 34AN XY: 135910
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GnomAD4 exome AF: 0.000211 AC: 309AN: 1461878Hom.: 1 Cov.: 32 AF XY: 0.000201 AC XY: 146AN XY: 727238
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GnomAD4 genome ? AF: 0.000781 AC: 119AN: 152288Hom.: 0 Cov.: 32 AF XY: 0.000725 AC XY: 54AN XY: 74466
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2022 | CLCN1: BP4, BP7 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 03, 2021 | - - |
Batten-Turner congenital myopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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 | Jan 31, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at