chrX-50067578-G-A

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

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.34
Variant links:
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
CLCN5NM_001127898.4 linkuse as main transcriptc.164-2301G>A intron_variant ENST00000376091.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CLCN5ENST00000376108.7 linkuse as main transcriptc.-230G>A 5_prime_UTR_variant 1/121 A1P51795-1
CLCN5ENST00000376091.8 linkuse as main transcriptc.164-2301G>A intron_variant 2 NM_001127898.4 P3P51795-2
CLCN5ENST00000376088.7 linkuse as main transcriptc.164-2301G>A intron_variant 2 P3P51795-2
CLCN5ENST00000643129.1 linkuse as main transcriptc.*261-2301G>A intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.000645
AC:
72
AN:
111691
Hom.:
0
Cov.:
23
AF XY:
0.000590
AC XY:
20
AN XY:
33891
show subpopulations
Gnomad AFR
AF:
0.0000325
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00258
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0210
Gnomad NFE
AF:
0.000677
Gnomad OTH
AF:
0.00201
GnomAD4 exome
AF:
0.000824
AC:
527
AN:
639899
Hom.:
0
Cov.:
18
AF XY:
0.000882
AC XY:
169
AN XY:
191517
show subpopulations
Gnomad4 AFR exome
AF:
0.000403
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000868
Gnomad4 OTH exome
AF:
0.000473
GnomAD4 genome
AF:
0.000644
AC:
72
AN:
111744
Hom.:
0
Cov.:
23
AF XY:
0.000589
AC XY:
20
AN XY:
33954
show subpopulations
Gnomad4 AFR
AF:
0.0000325
Gnomad4 AMR
AF:
0.00258
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000677
Gnomad4 OTH
AF:
0.00198
Alfa
AF:
0.000498
Hom.:
1
Bravo
AF:
0.00111

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 submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.32
CADD
Benign
19
DANN
Benign
0.94

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs781805006; hg19: chrX-49832233; API