rs150304865

Variant names:

• chr7-143316236-G-A
• rs150304865
• NM_000083.3:c.24G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-143316236-G-A
• chr7-143316236-G-C

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_000083.3(CLCN1):​c.24G>A​(p.Gln8Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000138 in 1,461,356 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: CLCN1 NM_000083.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.273
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• myotonia congenita, autosomal dominant

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• myotonia congenita, autosomal recessive

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• Thomsen and Becker disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 7-143316236-G-A is Benign according to our data. Variant chr7-143316236-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1106235.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.273 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000083.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLCN1	NM_000083.3	MANE Select	c.24G>A	p.Gln8Gln	synonymous	Exon 1 of 23	NP_000074.3	P35523
	CLCN1	NR_046453.2		n.126G>A		non_coding_transcript_exon	Exon 1 of 22

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLCN1	ENST00000343257.7	TSL:1 MANE Select	c.24G>A	p.Gln8Gln	synonymous	Exon 1 of 23	ENSP00000339867.2	P35523
	CLCN1	ENST00000650516.2		c.24G>A	p.Gln8Gln	synonymous	Exon 1 of 23	ENSP00000498052.2	A0A3B3IU72
	CLCN1	ENST00000958857.1		c.24G>A	p.Gln8Gln	synonymous	Exon 1 of 22	ENSP00000628916.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000798 AC: 20 AN: 250604 AF XY: 0.0000664

Gnomad AFR exome AF: 0.0000619

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000467

Gnomad NFE exome AF: 0.000159

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000138 AC: 202 AN: 1461356 Hom.: 0 Cov.: 32 AF XY: 0.000111 AC XY: 81 AN XY: 727004

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.0000940 AC: 5 AN: 53196

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.000174 AC: 193 AN: 1111736

Other (OTH) AF: 0.0000497 AC: 3 AN: 60378

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000907 Hom.: 0

Bravo AF: 0.0000151

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Congenital myotonia, autosomal recessive form;C2936781:Congenital myotonia, autosomal dominant form (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.4
DANN	Benign	0.64
PhyloP100		0.27
PromoterAI		-0.021	Neutral

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

Other links and lift over

dbSNP: rs150304865; hg19: chr7-143013329;