rs149316679
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6BS2_Supporting
The NM_000083.3(CLCN1):c.2230C>A(p.Pro744Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000237 in 1,613,700 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000083.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CLCN1 | NM_000083.3 | c.2230C>A | p.Pro744Thr | missense_variant | 18/23 | ENST00000343257.7 | |
CLCN1 | NR_046453.2 | n.2185C>A | non_coding_transcript_exon_variant | 17/22 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLCN1 | ENST00000343257.7 | c.2230C>A | p.Pro744Thr | missense_variant | 18/23 | 1 | NM_000083.3 | P4 | |
CLCN1 | ENST00000432192.6 | c.*1515C>A | 3_prime_UTR_variant, NMD_transcript_variant | 18/23 | 1 | ||||
CLCN1 | ENST00000650516.2 | c.2230C>A | p.Pro744Thr | missense_variant | 18/23 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000145 AC: 22AN: 151944Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000255 AC: 64AN: 251412Hom.: 0 AF XY: 0.000331 AC XY: 45AN XY: 135892
GnomAD4 exome AF: 0.000246 AC: 360AN: 1461638Hom.: 2 Cov.: 33 AF XY: 0.000274 AC XY: 199AN XY: 727146
GnomAD4 genome ? AF: 0.000145 AC: 22AN: 152062Hom.: 0 Cov.: 31 AF XY: 0.000108 AC XY: 8AN XY: 74318
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 16, 2021 | This variant is associated with the following publications: (PMID: 22649220) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Mar 13, 2023 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Feb 15, 2017 | - - |
Batten-Turner congenital myopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 28, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Congenital myotonia, autosomal recessive form;C2936781:Congenital myotonia, autosomal dominant form Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at