rs940864
Positions:
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_000083.3(CLCN1):c.1796+76A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 1,515,792 control chromosomes in the GnomAD database, including 133,522 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.44 ( 15213 hom., cov: 32)
Exomes 𝑓: 0.41 ( 118309 hom. )
Consequence
CLCN1
NM_000083.3 intron
NM_000083.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0860
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP6
?
Variant 7-143342218-A-G is Benign according to our data. Variant chr7-143342218-A-G is described in ClinVar as [Benign]. Clinvar id is 1255317.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CLCN1 | NM_000083.3 | c.1796+76A>G | intron_variant | ENST00000343257.7 | |||
CLCN1 | NR_046453.2 | n.1751+76A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLCN1 | ENST00000343257.7 | c.1796+76A>G | intron_variant | 1 | NM_000083.3 | P4 | |||
CLCN1 | ENST00000432192.6 | c.*1081+76A>G | intron_variant, NMD_transcript_variant | 1 | |||||
CLCN1 | ENST00000650516.2 | c.1796+76A>G | intron_variant | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.439 AC: 66641AN: 151864Hom.: 15179 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
66641
AN:
151864
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.414 AC: 564070AN: 1363810Hom.: 118309 Cov.: 21 AF XY: 0.414 AC XY: 282596AN XY: 682758
GnomAD4 exome
AF:
AC:
564070
AN:
1363810
Hom.:
Cov.:
21
AF XY:
AC XY:
282596
AN XY:
682758
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.439 AC: 66731AN: 151982Hom.: 15213 Cov.: 32 AF XY: 0.433 AC XY: 32198AN XY: 74284
GnomAD4 genome
?
AF:
AC:
66731
AN:
151982
Hom.:
Cov.:
32
AF XY:
AC XY:
32198
AN XY:
74284
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
1233
AN:
3478
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 26, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at