Variant X-10185110-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The ENST00000380833.9(CLCN4):c.78G>A(p.Thr26=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000159 in 1,208,033 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 72 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., 14 hem., cov: 23)

Exomes 𝑓: 0.00015 ( 0 hom. 58 hem. )

Consequence

CLCN4
ENST00000380833.9 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.73

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=-0.76).

BP6

Variant X-10185110-G-A is Benign according to our data. Variant chrX-10185110-G-A is described in ClinVar as [Benign]. Clinvar id is 697048.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-4.73 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000224 (25/111702) while in subpopulation EAS AF= 0.00253 (9/3562). AF 95% confidence interval is 0.00132. There are 0 homozygotes in gnomad4. There are 14 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 14 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLCN4	NM_001830.4 linkuse as main transcript	c.78G>A	p.Thr26=	synonymous_variant	3/13	ENST00000380833.9	NP_001821.2
CLCN4	NM_001256944.2 linkuse as main transcript	c.-38-9801G>A		intron_variant			NP_001243873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLCN4	ENST00000380833.9 linkuse as main transcript	c.78G>A	p.Thr26=	synonymous_variant	3/13	1	NM_001830.4	ENSP00000370213	P4	P51793-1

Frequencies

GnomAD3 genomes

AF:

0.000224

AC:

AN:

111649

Hom.:

Cov.:

AF XY:

0.000414

AC XY:

AN XY:

33845

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00252

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00182

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000941

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000482

AC:

AN:

182557

Hom.:

AF XY:

0.000507

AC XY:

AN XY:

67015

show subpopulations

Gnomad AFR exome

AF:

0.0000762

Gnomad AMR exome

AF:

0.0000368

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00247

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00250

Gnomad NFE exome

AF:

0.000135

Gnomad OTH exome

AF:

0.000222

GnomAD4 exome

AF:

0.000152

AC:

167

AN:

1096331

Hom.:

Cov.:

AF XY:

0.000160

AC XY:

AN XY:

361751

show subpopulations

Gnomad4 AFR exome

AF:

0.000114

Gnomad4 AMR exome

AF:

0.0000285

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00126

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00200

Gnomad4 NFE exome

AF:

0.0000369

Gnomad4 OTH exome

AF:

0.000261

GnomAD4 genome

AF:

0.000224

AC:

AN:

111702

Hom.:

Cov.:

AF XY:

0.000413

AC XY:

AN XY:

33908

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00253

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00182

Gnomad4 NFE

AF:

0.0000941

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000945

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 submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 24, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.40

DANN

Benign

0.89

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.

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