Variant 7-143316197-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000083.3(CLCN1):c.-16C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0029 in 1,455,416 control chromosomes in the GnomAD database, including 150 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0045 ( 11 hom., cov: 32)

Exomes 𝑓: 0.0029 ( 150 hom. )

Failed GnomAD Quality Control

Consequence

CLCN1
NM_000083.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.548

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:

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=-0.83).

BP6

Variant 7-143316197-C-G is Benign according to our data. Variant chr7-143316197-C-G is described in ClinVar as [Benign]. Clinvar id is 383610.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0703 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.-16C>G		5_prime_UTR_variant	1/23	ENST00000343257.7	NP_000074.3
CLCN1	NR_046453.2 linkuse as main transcript	n.87C>G		non_coding_transcript_exon_variant	1/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLCN1	ENST00000343257.7 linkuse as main transcript	c.-16C>G		5_prime_UTR_variant	1/23	1	NM_000083.3	ENSP00000339867	P4
CLCN1	ENST00000650516.2 linkuse as main transcript	c.-16C>G		5_prime_UTR_variant	1/23			ENSP00000498052	A2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

682

AN:

151748

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00123

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0362

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00836

Gnomad SAS

AF:

0.000830

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00962

GnomAD3 exomes

AF:

0.0117

AC:

2877

AN:

246616

Hom.:

118

AF XY:

0.00918

AC XY:

1228

AN XY:

133808

show subpopulations

Gnomad AFR exome

AF:

0.000881

Gnomad AMR exome

AF:

0.0761

Gnomad ASJ exome

AF:

0.000700

Gnomad EAS exome

AF:

0.00699

Gnomad SAS exome

AF:

0.000818

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000134

Gnomad OTH exome

AF:

0.0111

GnomAD4 exome

AF:

0.00290

AC:

4216

AN:

1455416

Hom.:

150

Cov.:

AF XY:

0.00261

AC XY:

1887

AN XY:

724196

show subpopulations

Gnomad4 AFR exome

AF:

0.000569

Gnomad4 AMR exome

AF:

0.0723

Gnomad4 ASJ exome

AF:

0.000574

Gnomad4 EAS exome

AF:

0.0151

Gnomad4 SAS exome

AF:

0.000882

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000108

Gnomad4 OTH exome

AF:

0.00246

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00448

AC:

681

AN:

151864

Hom.:

Cov.:

AF XY:

0.00477

AC XY:

354

AN XY:

74226

show subpopulations

Gnomad4 AFR

AF:

0.00123

Gnomad4 AMR

AF:

0.0361

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00838

Gnomad4 SAS

AF:

0.000831

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00952

Alfa

AF:

0.00411

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 31, 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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.41

DANN

Benign

0.69

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