chr7-143316245-T-C
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7
The NM_000083.3(CLCN1):c.33T>C(p.Gly11=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,612,286 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 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000018 ( 0 hom. )
Consequence
CLCN1
NM_000083.3 synonymous
NM_000083.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.16
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 -7 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
?
Variant 7-143316245-T-C is Benign according to our data. Variant chr7-143316245-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1632022.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-2.16 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CLCN1 | NM_000083.3 | c.33T>C | p.Gly11= | synonymous_variant | 1/23 | ENST00000343257.7 | |
CLCN1 | NR_046453.2 | n.135T>C | non_coding_transcript_exon_variant | 1/22 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLCN1 | ENST00000343257.7 | c.33T>C | p.Gly11= | synonymous_variant | 1/23 | 1 | NM_000083.3 | P4 | |
CLCN1 | ENST00000650516.2 | c.33T>C | p.Gly11= | synonymous_variant | 1/23 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000663 AC: 1AN: 150796Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000319 AC: 8AN: 250672Hom.: 0 AF XY: 0.0000517 AC XY: 7AN XY: 135526
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GnomAD4 exome AF: 0.0000178 AC: 26AN: 1461490Hom.: 0 Cov.: 32 AF XY: 0.0000261 AC XY: 19AN XY: 727066
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GnomAD4 genome ? AF: 0.00000663 AC: 1AN: 150796Hom.: 0 Cov.: 32 AF XY: 0.0000136 AC XY: 1AN XY: 73564
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Congenital myotonia, autosomal recessive form;C2936781:Congenital myotonia, autosomal dominant form Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 30, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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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