Variant rs143534990 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_001830.4(CLCN4):c.747G>A(p.Glu249=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00033 in 1,209,156 control chromosomes in the GnomAD database, including 1 homozygotes. There are 128 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 0.00036 ( 0 hom., 15 hem., cov: 23)

Exomes 𝑓: 0.00033 ( 1 hom. 113 hem. )

Consequence

CLCN4
NM_001830.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.11

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant X-10206549-G-A is Benign according to our data. Variant chrX-10206549-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 415736.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.11 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 15 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLCN4	NM_001830.4 linkuse as main transcript	c.747G>A	p.Glu249=	synonymous_variant	7/13	ENST00000380833.9	NP_001821.2
CLCN4	NM_001256944.2 linkuse as main transcript	c.465G>A	p.Glu155=	synonymous_variant	5/11		NP_001243873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLCN4	ENST00000380833.9 linkuse as main transcript	c.747G>A	p.Glu249=	synonymous_variant	7/13	1	NM_001830.4	ENSP00000370213	P4	P51793-1

Frequencies

GnomAD3 genomes

AF:

0.000364

AC:

AN:

112755

Hom.:

Cov.:

AF XY:

0.000430

AC XY:

AN XY:

34899

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000373

Gnomad ASJ

AF:

0.0124

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000750

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000598

AC:

106

AN:

177281

Hom.:

AF XY:

0.000466

AC XY:

AN XY:

62191

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000297

Gnomad ASJ exome

AF:

0.0107

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000204

Gnomad OTH exome

AF:

0.000686

GnomAD4 exome

AF:

0.000327

AC:

358

AN:

1096401

Hom.:

Cov.:

AF XY:

0.000312

AC XY:

113

AN XY:

361855

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000229

Gnomad4 ASJ exome

AF:

0.0115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000939

Gnomad4 OTH exome

AF:

0.00106

GnomAD4 genome

AF:

0.000364

AC:

AN:

112755

Hom.:

Cov.:

AF XY:

0.000430

AC XY:

AN XY:

34899

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000373

Gnomad4 ASJ

AF:

0.0124

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000750

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00204

Hom.:

Bravo

AF:

0.000476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 15, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2023	CLCN4: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

8.3

DANN

Benign

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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