rs2272252

Positions:

chr7-143339244-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000083.3(CLCN1):c.1402-9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 1,578,338 control chromosomes in the GnomAD database, including 136,568 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 15197 hom., cov: 32)

Exomes 𝑓: 0.41 ( 121371 hom. )

Consequence

CLCN1
NM_000083.3 intron

Scores

Splicing: ADA: 0.00001508

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.584

Variant links:

Genes affected

CLCN1 (HGNC:2019): (chloride voltage-gated channel 1) 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. The protein encoded by this gene regulates the electric excitability of the skeletal muscle membrane. Mutations in this gene cause two forms of inherited human muscle disorders: recessive generalized myotonia congenita (Becker) and dominant myotonia (Thomsen). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2012]

CLCN1 links:

CLCN1 (HGNC:):

CLCN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 7-143339244-C-T is Benign according to our data. Variant chr7-143339244-C-T is described in ClinVar as [Benign]. Clinvar id is 359111.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-143339244-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLCN1	NM_000083.3 linkuse as main transcript	c.1402-9C>T		intron_variant		ENST00000343257.7	NP_000074.3	P35523
CLCN1	NR_046453.2 linkuse as main transcript	n.1357-9C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
CLCN1	ENST00000343257.7 linkuse as main transcript	c.1402-9C>T	intron_variant	1	NM_000083.3	ENSP00000339867.2	P35523
CLCN1	ENST00000432192.6 linkuse as main transcript	n.*687-9C>T	intron_variant	1		ENSP00000395949.2	H7C0N6
CLCN1	ENST00000650516.2 linkuse as main transcript	c.1402-9C>T	intron_variant			ENSP00000498052.2	A0A3B3IU72

Frequencies

GnomAD3 genomes

AF:

0.438

AC:

66598

AN:

151958

Hom.:

15163

Cov.:

show subpopulations

Gnomad AFR

AF:

0.560

Gnomad AMI

AF:

0.206

Gnomad AMR

AF:

0.338

Gnomad ASJ

AF:

0.513

Gnomad EAS

AF:

0.270

Gnomad SAS

AF:

0.405

Gnomad FIN

AF:

0.373

Gnomad MID

AF:

0.484

Gnomad NFE

AF:

0.411

Gnomad OTH

AF:

0.450

GnomAD3 exomes

AF:

0.401

AC:

100807

AN:

251474

Hom.:

21050

AF XY:

0.402

AC XY:

54674

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.571

Gnomad AMR exome

AF:

0.304

Gnomad ASJ exome

AF:

0.505

Gnomad EAS exome

AF:

0.259

Gnomad SAS exome

AF:

0.418

Gnomad FIN exome

AF:

0.382

Gnomad NFE exome

AF:

0.418

Gnomad OTH exome

AF:

0.422

GnomAD4 exome

AF:

0.409

AC:

583403

AN:

1426262

Hom.:

121371

Cov.:

AF XY:

0.410

AC XY:

291601

AN XY:

711868

show subpopulations

Gnomad4 AFR exome

AF:

0.561

Gnomad4 AMR exome

AF:

0.310

Gnomad4 ASJ exome

AF:

0.500

Gnomad4 EAS exome

AF:

0.304

Gnomad4 SAS exome

AF:

0.417

Gnomad4 FIN exome

AF:

0.387

Gnomad4 NFE exome

AF:

0.410

Gnomad4 OTH exome

AF:

0.424

GnomAD4 genome

AF:

0.439

AC:

66688

AN:

152076

Hom.:

15197

Cov.:

AF XY:

0.433

AC XY:

32174

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.560

Gnomad4 AMR

AF:

0.338

Gnomad4 ASJ

AF:

0.513

Gnomad4 EAS

AF:

0.271

Gnomad4 SAS

AF:

0.406

Gnomad4 FIN

AF:

0.373

Gnomad4 NFE

AF:

0.411

Gnomad4 OTH

AF:

0.447

Alfa

AF:

0.428

Hom.:

8843

Bravo

AF:

0.441

Asia WGS

AF:

0.352

AC:

1230

AN:

3478

EpiCase

AF:

0.424

EpiControl

AF:

0.426

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 22, 2021	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 28, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Batten-Turner congenital myopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Congenital myotonia, autosomal recessive form;C2936781:Congenital myotonia, autosomal dominant form

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Congenital myotonia, autosomal dominant form

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Congenital myotonia, autosomal recessive form

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.2

DANN

Benign

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000015

dbscSNV1_RF

Benign

0.0

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