rs143437511

Variant names:

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001830.4(CLCN4):c.1758G>A(p.Val586Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00422 in 1,210,610 control chromosomes in the GnomAD database, including 10 homozygotes. There are 1,621 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 0.0028 ( 0 hom., 80 hem., cov: 24)

Exomes 𝑓: 0.0044 ( 10 hom. 1541 hem. )

Consequence

CLCN4
NM_001830.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.420

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]

CLCN4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant X-10213862-G-A is Benign according to our data. Variant chrX-10213862-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 210732.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-10213862-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.42 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 80 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLCN4	NM_001830.4 link	c.1758G>A	p.Val586Val	synonymous_variant	Exon 11 of 13	ENST00000380833.9	NP_001821.2	P51793-1
CLCN4	NM_001256944.2 link	c.1476G>A	p.Val492Val	synonymous_variant	Exon 9 of 11		NP_001243873.1	P51793-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLCN4	ENST00000380833.9 link	c.1758G>A	p.Val586Val	synonymous_variant	Exon 11 of 13	1	NM_001830.4	ENSP00000370213.4		P51793-1

Frequencies

GnomAD3 genomes

AF:

0.00275

AC:

310

AN:

112572

Hom.:

Cov.:

AF XY:

0.00228

AC XY:

AN XY:

34722

show subpopulations

Gnomad AFR

AF:

0.000581

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000280

Gnomad ASJ

AF:

0.00452

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000367

Gnomad FIN

AF:

0.00162

Gnomad MID

AF:

0.00833

Gnomad NFE

AF:

0.00486

Gnomad OTH

AF:

0.00328

GnomAD3 exomes

AF:

0.00290

AC:

530

AN:

182910

Hom.:

AF XY:

0.00300

AC XY:

202

AN XY:

67426

show subpopulations

Gnomad AFR exome

AF:

0.000380

Gnomad AMR exome

AF:

0.000803

Gnomad ASJ exome

AF:

0.00577

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000157

Gnomad FIN exome

AF:

0.00238

Gnomad NFE exome

AF:

0.00496

Gnomad OTH exome

AF:

0.00332

GnomAD4 exome

AF:

0.00437

AC:

4793

AN:

1097983

Hom.:

Cov.:

AF XY:

0.00424

AC XY:

1541

AN XY:

363345

show subpopulations

Gnomad4 AFR exome

AF:

0.000644

Gnomad4 AMR exome

AF:

0.00102

Gnomad4 ASJ exome

AF:

0.00557

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000388

Gnomad4 FIN exome

AF:

0.00284

Gnomad4 NFE exome

AF:

0.00511

Gnomad4 OTH exome

AF:

0.00371

GnomAD4 genome

AF:

0.00276

AC:

311

AN:

112627

Hom.:

Cov.:

AF XY:

0.00230

AC XY:

AN XY:

34787

show subpopulations

Gnomad4 AFR

AF:

0.000580

Gnomad4 AMR

AF:

0.000280

Gnomad4 ASJ

AF:

0.00452

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000368

Gnomad4 FIN

AF:

0.00162

Gnomad4 NFE

AF:

0.00488

Gnomad4 OTH

AF:

0.00324

Alfa

AF:

0.00418

Hom.:

Bravo

AF:

0.00241

EpiCase

AF:

0.00469

EpiControl

AF:

0.00534

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Dec 12, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

Dec 19, 2018

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Intellectual disability, X-linked 49

Benign:1

Feb 09, 2022

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

1.6

DANN

Benign

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over