X-10185083-C-T
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2
The NM_001830.4(CLCN4):c.51C>T(p.Leu17=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000298 in 1,207,309 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 13 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.000045 ( 0 hom., 1 hem., cov: 23)
Exomes 𝑓: 0.000028 ( 0 hom. 12 hem. )
Consequence
CLCN4
NM_001830.4 synonymous
NM_001830.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.305
Genes affected
CLCN4 (HGNC:2022): (chloride voltage-gated channel 4) 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. Chloride channel 4 has an evolutionary conserved CpG island and is conserved in both mouse and hamster. This gene is mapped in close proximity to APXL (Apical protein Xenopus laevis-like) and OA1 (Ocular albinism type I), which are both located on the human X chromosome at band p22.3. The physiological role of chloride channel 4 remains unknown but may contribute to the pathogenesis of neuronal disorders. Alternate splicing results in two transcript variants that encode different proteins. [provided by RefSeq, Mar 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.27).
BP6
Variant X-10185083-C-T is Benign according to our data. Variant chrX-10185083-C-T is described in ClinVar as [Benign]. Clinvar id is 1165880.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.305 with no splicing effect.
BS2
High Hemizygotes in GnomAdExome4 at 12 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CLCN4 | NM_001830.4 | c.51C>T | p.Leu17= | synonymous_variant | 3/13 | ENST00000380833.9 | NP_001821.2 | |
CLCN4 | NM_001256944.2 | c.-38-9828C>T | intron_variant | NP_001243873.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CLCN4 | ENST00000380833.9 | c.51C>T | p.Leu17= | synonymous_variant | 3/13 | 1 | NM_001830.4 | ENSP00000370213 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000449 AC: 5AN: 111326Hom.: 0 Cov.: 23 AF XY: 0.0000298 AC XY: 1AN XY: 33554
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GnomAD3 exomes AF: 0.0000438 AC: 8AN: 182576Hom.: 0 AF XY: 0.0000448 AC XY: 3AN XY: 67034
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GnomAD4 exome AF: 0.0000283 AC: 31AN: 1095930Hom.: 0 Cov.: 29 AF XY: 0.0000332 AC XY: 12AN XY: 361366
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GnomAD4 genome AF: 0.0000449 AC: 5AN: 111379Hom.: 0 Cov.: 23 AF XY: 0.0000297 AC XY: 1AN XY: 33617
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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 | Labcorp Genetics (formerly Invitae), Labcorp | Jan 05, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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