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GeneBe

X-10185083-C-T

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 (★). Synonymous variant affecting the same amino acid position (i.e. L17L) has been classified as Likely 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

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.305
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.27).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.305 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Hemizygotes in GnomAdExome at 3 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CLCN4NM_001830.4 linkuse as main transcriptc.51C>T p.Leu17= synonymous_variant 3/13 ENST00000380833.9
CLCN4NM_001256944.2 linkuse as main transcriptc.-38-9828C>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CLCN4ENST00000380833.9 linkuse as main transcriptc.51C>T p.Leu17= synonymous_variant 3/131 NM_001830.4 P4P51793-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0000449
AC:
5
AN:
111326
Hom.:
0
Cov.:
23
AF XY:
0.0000298
AC XY:
1
AN XY:
33554
show subpopulations
Gnomad AFR
AF:
0.0000655
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000953
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000377
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000438
AC:
8
AN:
182576
Hom.:
0
AF XY:
0.0000448
AC XY:
3
AN XY:
67034
show subpopulations
Gnomad AFR exome
AF:
0.0000761
Gnomad AMR exome
AF:
0.000184
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000245
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000283
AC:
31
AN:
1095930
Hom.:
0
Cov.:
29
AF XY:
0.0000332
AC XY:
12
AN XY:
361366
show subpopulations
Gnomad4 AFR exome
AF:
0.0000379
Gnomad4 AMR exome
AF:
0.0000854
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:
0.0000321
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0000449
AC:
5
AN:
111379
Hom.:
0
Cov.:
23
AF XY:
0.0000297
AC XY:
1
AN XY:
33617
show subpopulations
Gnomad4 AFR
AF:
0.0000654
Gnomad4 AMR
AF:
0.0000952
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000377
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000227

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 submitterclinical testingInvitaeJan 05, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.27
Cadd
Benign
2.3
Dann
Benign
0.80

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: rs139365114; hg19: chrX-10153123; API