7-143316199-C-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_000083.3(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 NM_000083.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.11

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]

ACMG classification

Verdict is Benign. Variant got -10 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_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 122 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLCN1	NM_000083.3	c.-14C>A		5_prime_UTR_variant	1/23	ENST00000343257.7
CLCN1	NR_046453.2	n.89C>A		non_coding_transcript_exon_variant	1/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLCN1	ENST00000343257.7	c.-14C>A		5_prime_UTR_variant	1/23	1	NM_000083.3	P4
CLCN1	ENST00000650516.2	c.-14C>A		5_prime_UTR_variant	1/23			A2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 690 AN: 147794 Hom.: 11 Cov.: 32 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

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.: 32 AF XY: 0.00261 AC XY: 1891 AN XY: 723312

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.: 11 Cov.: 32 AF XY: 0.00493 AC XY: 355 AN XY: 72048

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.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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. -

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

Other links and lift over

dbSNP: rs2280663; hg19: chr7-143013292;