rs78085922
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000083.3(CLCN1):c.2244G>A(p.Leu748=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0134 in 1,613,444 control chromosomes in the GnomAD database, including 218 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L748L) has been classified as Likely benign.
Frequency
Consequence
NM_000083.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CLCN1 | NM_000083.3 | c.2244G>A | p.Leu748= | synonymous_variant | 18/23 | ENST00000343257.7 | |
CLCN1 | NR_046453.2 | n.2199G>A | non_coding_transcript_exon_variant | 17/22 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLCN1 | ENST00000343257.7 | c.2244G>A | p.Leu748= | synonymous_variant | 18/23 | 1 | NM_000083.3 | P4 | |
CLCN1 | ENST00000432192.6 | c.*1529G>A | 3_prime_UTR_variant, NMD_transcript_variant | 18/23 | 1 | ||||
CLCN1 | ENST00000650516.2 | c.2244G>A | p.Leu748= | synonymous_variant | 18/23 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0172 AC: 2607AN: 151968Hom.: 43 Cov.: 31
GnomAD3 exomes AF: 0.0130 AC: 3258AN: 251308Hom.: 33 AF XY: 0.0127 AC XY: 1722AN XY: 135852
GnomAD4 exome AF: 0.0131 AC: 19081AN: 1461358Hom.: 175 Cov.: 33 AF XY: 0.0128 AC XY: 9338AN XY: 727014
GnomAD4 genome ? AF: 0.0171 AC: 2608AN: 152086Hom.: 43 Cov.: 31 AF XY: 0.0163 AC XY: 1215AN XY: 74348
ClinVar
Submissions by phenotype
not specified Benign:4
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Apr 15, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 03, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Batten-Turner congenital myopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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