rs55681486

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000080.4(CHRNE):c.1305A>G(p.Arg435Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0845 in 1,607,470 control chromosomes in the GnomAD database, including 6,198 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. R435R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.073 ( 465 hom., cov: 32)

Exomes 𝑓: 0.086 ( 5733 hom. )

Consequence

CHRNE
NM_000080.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.847

Publications

11 publications found

Variant links:

Genes affected

CHRNE (HGNC:1966): (cholinergic receptor nicotinic epsilon subunit) Acetylcholine receptors at mature mammalian neuromuscular junctions are pentameric protein complexes composed of four subunits in the ratio of two alpha subunits to one beta, one epsilon, and one delta subunit. The acetylcholine receptor changes subunit composition shortly after birth when the epsilon subunit replaces the gamma subunit seen in embryonic receptors. Mutations in the epsilon subunit are associated with congenital myasthenic syndrome. [provided by RefSeq, Sep 2009]

CHRNE Gene-Disease associations (from GenCC):

congenital myasthenic syndrome
Inheritance: AR Classification: DEFINITIVE Submitted by: Illumina
congenital myasthenic syndrome 4A
Inheritance: AD, AR Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), PanelApp Australia
congenital myasthenic syndrome 4B
Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), PanelApp Australia
congenital myasthenic syndrome 4C
Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
postsynaptic congenital myasthenic syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CHRNE links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 17-4899022-T-C is Benign according to our data. Variant chr17-4899022-T-C is described in ClinVar as Benign. ClinVar VariationId is 128763.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.847 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNE	NM_000080.4 link	c.1305A>G	p.Arg435Arg	synonymous_variant	Exon 11 of 12	ENST00000649488.2	NP_000071.1
CHRNE	XM_017024115.2 link	c.1269A>G	p.Arg423Arg	synonymous_variant	Exon 12 of 13		XP_016879604.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
CHRNE	ENST00000649488.2 link	c.1305A>G	p.Arg435Arg	synonymous_variant	Exon 11 of 12		NM_000080.4	ENSP00000497829.1
CHRNE	ENST00000649830.1 link	c.372A>G	p.Arg124Arg	synonymous_variant	Exon 11 of 11			ENSP00000496907.1
CHRNE	ENST00000572438.1 link	n.991A>G		non_coding_transcript_exon_variant	Exon 6 of 7	5
CHRNE	ENST00000652550.1 link	n.1035A>G		non_coding_transcript_exon_variant	Exon 3 of 4

Frequencies

GnomAD3 genomes

AF:

0.0734

AC:

11156

AN:

152056

Hom.:

464

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0317

Gnomad AMI

AF:

0.116

Gnomad AMR

AF:

0.0603

Gnomad ASJ

AF:

0.0646

Gnomad EAS

AF:

0.0608

Gnomad SAS

AF:

0.0361

Gnomad FIN

AF:

0.145

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0944

Gnomad OTH

AF:

0.0593

GnomAD2 exomes

AF:

0.0749

AC:

17689

AN:

236078

AF XY:

0.0749

show subpopulations

Gnomad AFR exome

AF:

0.0278

Gnomad AMR exome

AF:

0.0466

Gnomad ASJ exome

AF:

0.0593

Gnomad EAS exome

AF:

0.0567

Gnomad FIN exome

AF:

0.138

Gnomad NFE exome

AF:

0.0952

Gnomad OTH exome

AF:

0.0806

GnomAD4 exome

AF:

0.0857

AC:

124667

AN:

1455294

Hom.:

5733

Cov.:

AF XY:

0.0844

AC XY:

61027

AN XY:

723308

show subpopulations

African (AFR)

AF:

0.0279

AC:

934

AN:

33436

American (AMR)

AF:

0.0476

AC:

2095

AN:

44050

Ashkenazi Jewish (ASJ)

AF:

0.0594

AC:

1540

AN:

25946

East Asian (EAS)

AF:

0.0805

AC:

3184

AN:

39540

South Asian (SAS)

AF:

0.0305

AC:

2595

AN:

84944

European-Finnish (FIN)

AF:

0.136

AC:

6997

AN:

51628

Middle Eastern (MID)

AF:

0.0623

AC:

359

AN:

5758

European-Non Finnish (NFE)

AF:

0.0923

AC:

102423

AN:

1109854

Other (OTH)

AF:

0.0755

AC:

4540

AN:

60138

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

7218

14435

21653

28870

36088

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3616

7232

10848

14464

18080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0733

AC:

11155

AN:

152176

Hom.:

465

Cov.:

AF XY:

0.0751

AC XY:

5585

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.0317

AC:

1318

AN:

41542

American (AMR)

AF:

0.0602

AC:

921

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0646

AC:

224

AN:

3470

East Asian (EAS)

AF:

0.0609

AC:

314

AN:

5152

South Asian (SAS)

AF:

0.0361

AC:

174

AN:

4822

European-Finnish (FIN)

AF:

0.145

AC:

1533

AN:

10588

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0944

AC:

6418

AN:

67990

Other (OTH)

AF:

0.0582

AC:

123

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

528

1057

1585

2114

2642

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

252

378

504

630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0832

Hom.:

186

Bravo

AF:

0.0634

Asia WGS

AF:

0.0410

AC:

142

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Jun 23, 2025

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 29, 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. -

Aug 15, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Congenital myasthenic syndrome

Benign:2

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Congenital myasthenic syndrome 4A

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

-0.83

CADD

Benign

6.8

(source)

DANN

Benign

0.75

PhyloP100

-0.85

PromoterAI

-0.054

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over