Genetic Variant ENST00000343257:c.-14C>A (chr7-143316199-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The ENST00000343257(CLCN1):c.-14C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0047 ( 11 hom., cov: 32)

Exomes 𝑓: 0.0029 ( 157 hom. )

Failed GnomAD Quality Control

Consequence

CLCN1
ENST00000343257 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.11

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 7-143316199-C-A is Benign according to our data. Variant chr7-143316199-C-A is described in ClinVar as [Benign]. Clinvar id is 383612.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLCN1	NM_000083.3 link	c.-14C>A		5_prime_UTR_variant	Exon 1 of 23	ENST00000343257.7	NP_000074.3	P35523
CLCN1	NR_046453.2 link	n.89C>A		non_coding_transcript_exon_variant	Exon 1 of 22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLCN1	ENST00000343257 link	c.-14C>A		5_prime_UTR_variant	Exon 1 of 23	1	NM_000083.3	ENSP00000339867.2		P35523
CLCN1	ENST00000650516 link	c.-14C>A		5_prime_UTR_variant	Exon 1 of 23			ENSP00000498052.2		A0A3B3IU72

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

690

AN:

147794

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00127

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0376

Gnomad ASJ

AF:

0.000580

Gnomad EAS

AF:

0.00832

Gnomad SAS

AF:

0.00106

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000193

Gnomad OTH

AF:

0.00987

GnomAD3 exomes

AF:

0.0117

AC:

2883

AN:

246368

Hom.:

122

AF XY:

0.00922

AC XY:

1233

AN XY:

133754

show subpopulations

Gnomad AFR exome

AF:

0.000881

Gnomad AMR exome

AF:

0.0763

Gnomad ASJ exome

AF:

0.000702

Gnomad EAS exome

AF:

0.00704

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00291

AC:

4226

AN:

1453328

Hom.:

157

Cov.:

AF XY:

0.00261

AC XY:

1891

AN XY:

723312

show subpopulations

Gnomad4 AFR exome

AF:

0.000569

Gnomad4 AMR exome

AF:

0.0726

Gnomad4 ASJ exome

AF:

0.000575

Gnomad4 EAS exome

AF:

0.0151

Gnomad4 SAS exome

AF:

0.000883

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:

0.00466

AC:

689

AN:

147886

Hom.:

Cov.:

AF XY:

0.00493

AC XY:

355

AN XY:

72048

show subpopulations

Gnomad4 AFR

AF:

0.00127

Gnomad4 AMR

AF:

0.0375

Gnomad4 ASJ

AF:

0.000580

Gnomad4 EAS

AF:

0.00834

Gnomad4 SAS

AF:

0.00107

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000193

Gnomad4 OTH

AF:

0.00977

Alfa

AF:

0.000783

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Oct 31, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.088

DANN

Benign

0.67

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