chr7-143320714-G-T
Variant names:
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBA1
The NM_000083.3(CLCN1):c.352G>T(p.Gly118Trp) variant causes a missense change. The variant allele was found at a frequency of 0.977 in 1,613,664 control chromosomes in the GnomAD database, including 769,979 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.98 ( 73648 hom., cov: 29)
Exomes 𝑓: 0.98 ( 696331 hom. )
Consequence
CLCN1
NM_000083.3 missense
NM_000083.3 missense
Scores
2
16
Clinical Significance
Conservation
PhyloP100: 6.18
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 -18 ACMG points.
PM1
In a helix (size 34) in uniprot entity CLCN1_HUMAN there are 9 pathogenic changes around while only 0 benign (100%) in NM_000083.3
BP4
Computational evidence support a benign effect (MetaRNN=5.607244E-7).
BP6
Variant 7-143320714-G-T is Benign according to our data. Variant chr7-143320714-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 802378.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-143320714-G-T is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.987 is higher than 0.05.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CLCN1 | ENST00000343257.7 | c.352G>T | p.Gly118Trp | missense_variant | Exon 3 of 23 | 1 | NM_000083.3 | ENSP00000339867.2 | ||
CLCN1 | ENST00000432192.6 | n.118G>T | non_coding_transcript_exon_variant | Exon 2 of 23 | 1 | ENSP00000395949.2 | ||||
CLCN1 | ENST00000650516.2 | c.352G>T | p.Gly118Trp | missense_variant | Exon 3 of 23 | ENSP00000498052.2 |
Frequencies
GnomAD3 genomes AF: 0.984 AC: 149559AN: 152008Hom.: 73590 Cov.: 29
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GnomAD3 exomes AF: 0.985 AC: 247777AN: 251494Hom.: 122083 AF XY: 0.985 AC XY: 133910AN XY: 135922
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GnomAD4 exome AF: 0.976 AC: 1426547AN: 1461538Hom.: 696331 Cov.: 39 AF XY: 0.977 AC XY: 710223AN XY: 727110
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GnomAD4 genome AF: 0.984 AC: 149676AN: 152126Hom.: 73648 Cov.: 29 AF XY: 0.985 AC XY: 73258AN XY: 74354
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Congenital myotonia, autosomal recessive form;C2936781:Congenital myotonia, autosomal dominant form Benign:2
Likely benign, criteria provided, single submitter | research | Department Of Human Genetics, Institute Of Clinical And Translational Research, Biomedical Research Center, Slovak Academy Of Sciences | - | Almost all patients from our cohort were homozygous for this variant c.352G>T (p.(Gly118Trp)), indicating that T represents a wild-type allele. We identified only one patient homozygous for allele G, who, however, was homozygous also for the Likely Pathogenic variant c.959A>C (p.(Ala320Val)). Only according to the publication PMID: 23152584, c.352G>T variant can have a weak effect. - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 03, 2025 | - - |
Congenital myotonia, autosomal recessive form Benign:2
Benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 22, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Congenital myotonia, autosomal dominant form Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 22, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;N
PrimateAI
Uncertain
T
PROVEAN
Benign
.;N
REVEL
Uncertain
Sift
Benign
.;T
Sift4G
Benign
.;T
Polyphen
0.0
.;B
Vest4
0.091
MPC
0.22
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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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