chrX-50067578-G-A
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2
The ENST00000376108.7(CLCN5):c.-230G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000797 in 751,643 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 189 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00064 ( 0 hom., 20 hem., cov: 23)
Exomes 𝑓: 0.00082 ( 0 hom. 169 hem. )
Consequence
CLCN5
ENST00000376108.7 5_prime_UTR
ENST00000376108.7 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.34
Genes affected
CLCN5 (HGNC:2023): (chloride voltage-gated channel 5) This gene encodes a member of the ClC family of chloride ion channels and ion transporters. The encoded protein is primarily localized to endosomal membranes and may function to facilitate albumin uptake by the renal proximal tubule. Mutations in this gene have been found in Dent disease and renal tubular disorders complicated by nephrolithiasis. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.32).
BP6
Variant X-50067578-G-A is Benign according to our data. Variant chrX-50067578-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 368470.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000644 (72/111744) while in subpopulation AMR AF= 0.00258 (27/10485). AF 95% confidence interval is 0.00182. There are 0 homozygotes in gnomad4. There are 20 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
BS2
High Hemizygotes in GnomAd4 at 20 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CLCN5 | NM_001127898.4 | c.164-2301G>A | intron_variant | ENST00000376091.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLCN5 | ENST00000376108.7 | c.-230G>A | 5_prime_UTR_variant | 1/12 | 1 | A1 | |||
CLCN5 | ENST00000376091.8 | c.164-2301G>A | intron_variant | 2 | NM_001127898.4 | P3 | |||
CLCN5 | ENST00000376088.7 | c.164-2301G>A | intron_variant | 2 | P3 | ||||
CLCN5 | ENST00000643129.1 | c.*261-2301G>A | intron_variant, NMD_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.000645 AC: 72AN: 111691Hom.: 0 Cov.: 23 AF XY: 0.000590 AC XY: 20AN XY: 33891
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GnomAD4 exome AF: 0.000824 AC: 527AN: 639899Hom.: 0 Cov.: 18 AF XY: 0.000882 AC XY: 169AN XY: 191517
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GnomAD4 genome AF: 0.000644 AC: 72AN: 111744Hom.: 0 Cov.: 23 AF XY: 0.000589 AC XY: 20AN XY: 33954
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Dent disease Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at